Poly(diallylamine)-based bile acid sequestrants

ABSTRACT

The present invention relates to a method for removing bile acids from a patient and certain polymers of use in the method. The method comprises the step of administering to the patient a therapeutically effective amount of a polymer composition which includes a a poly(diallylamine) polymer which is substituted with hydrophobic groups. The hydrophobic groups can be a substituted or unsubstituted, straight chain or branched C 3 -C 24 -alkyl group, an aralkyl group or an aryl group.

RELATED APPLICATIONS

[0001] This application is a Continuation of U.S. application Ser. No.09/286,341, filed Apr. 5, 1999, which is a Continuation of InternationalApplication No. PCT/US97/23899, which designated the United States andwas filed on Dec. 29, 1997, published in English and which is aContinuation-in-Part of U.S. Ser. No. 08/777,408, filed Dec. 30, 1996,now U.S. Pat. No. 6,203,785. The entire teachings of the aboveapplications are incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] Salts of bile acids act as detergents to solubilize and,consequently, aid in the digestion of, dietary fats. Bile acids arederived from cholesterol. Following digestion, bile acids can bepassively absorbed in the jejunum or reabsorbed by active transport inthe ileum. Bile acids which are not reabsorbed are deconjugated anddehydroxylated by bacterial action in the distal ileum and largeintestine.

[0003] Reabsorption of bile acids from the intestine conserveslipoprotein cholesterol in the bloodstream. Conversely, the bloodcholesterol level can be reduced by hindering reabsorption of bileacids.

[0004] One method of reducing the amount of bile acids that arereabsorbed is oral administration of compounds that sequester the bileacids and cannot themselves be absorbed. The sequestered bile acidsconsequently are excreted. Serum cholesterol is then employed to producemore bile acids, thereby lowering the serum cholesterol level of thepatient.

SUMMARY OF THE INVENTION

[0005] The present invention relates to a method for removing bile acidsfrom a patient as well as certain polymers for use in the method. Themethod comprises the step of administering to the patient atherapeutically effective amount of a polymer characterized by adiallylamine monomer wherein the amino nitrogen atom bears at least onehydrophobic substituent. The hydrophobic substituent can be asubstituted or unsubstituted, straight chain or branched C₃-C₂₄-alkylgroup, a substituted or unsubstituted arylalkyl group or a substitutedor unsubstituted aryl group. The polymer to be administered can behomopolymer or a copolymer.

[0006] In one embodiment, the polymer to be administered is acrosslinked or linear poly(diallylamine) polymer wherein at least 10% ofthe amino nitrogen atoms are substituted by a C₃-C₂₄-alkyl group. Inanother embodiment, the polymer to be administered is characterized by adiallylamine monomer wherein the amino nitrogen atom bears an alkylgroup which is substituted with a quaternary ammonium group. Thenitrogen atom of the ammonium group can bear at least one terminalhydrophobic substituent.

[0007] The polymer to be administered can comprise secondary aminogroups, tertiary amino groups or quaternary ammonium groups or acombination thereof. Polymers which comprise secondary or tertiary aminogroups can also be administered in the form of salts of apharmaceutically acceptable acid.

[0008] The polymer can be linear or crosslinked. In one embodiment, thepolymer is crosslinked via the incorporation of a multifunctionalcomonomer. In another embodiment, the polymer is crosslinked viabridging groups which link amino nitrogen atoms on different polymerstrands.

[0009] In another embodiment, the invention relates topoly(diallylamine) polymers which are useful as bile acid sequestrants.These polymers are characterized by an diallylamine monomer, or repeatunit, wherein the amino nitrogen bears an alkyl substituent which issubstituted with an ammonium group. The polymer can be a homopolymer ora copolymer.

[0010] The present invention offers the advantage that both substitutedand unsubstituted diallylamines are readily polymerized and crosslinked,in comparison to other amine monomers. Such polymers also provideimproved efficacy over polymers utilized in prior art methods.

DETAILED DESCRIPTION OF THE INVENTION

[0011] The features and other details of the invention will now be moreparticularly described and pointed out in the claims. It will beunderstood that the particular embodiments of the invention are shown byway of illustration and not as limitations of the invention. Theprincipal features of the invention can be employed in variousembodiments without departing from the scope of the present invention.

[0012] The present invention is based on Applicants' discovery thatpoly(diallylamine) polymers comprising hydrophobic groups exhibitexcellent bile acid sequestration activity. The invention provides amethod for removing bile acids from a patient comprising administeringto the patient a therapeutically effective amount of a polymercharacterized by a diallylamine monomer, or repeat unit, wherein theamino nitrogen atom bears a hydrophobic substituent.

[0013] As used herein, the term “therapeutically effective amount”refers to an amount which is sufficient to remove a significant quantityof bile acids from the patient and, thus, to lower the serum cholesterollevel of the patient. The patient can be an animal, for example, amammal, or a human.

[0014] A “hydrophobic substituent”, as the term is used herein, is amoiety which, as a separate entity, is more soluble in octanol thanwater. For example, the octyl (C₈H₁₇) group is hydrophobic because itsparent alkane, octane, has greater solubility in octanol than in water.The hydrophobic substituent can be a saturated or unsaturated,substituted or unsubstituted hydrocarbon group. Such groups includesusbstituted and unsubstituted, normal, branched or cyclic alkyl groupshaving 3 or more carbon atoms, substituted or unsubstituted arylalkyl orheteroarylalkyl groups and substituted or unsubstituted aryl orheteroaryl groups.

[0015] In one embodiment, the polymer to be administered is apoly(diallylamine) polymer characterized by a diallylamine monomerwherein the amino nitrogen atom bears at least one hydrophobicsubstituent selected from the group consisting of substituted orunsubstituted, normal, branched or cyclic C₃-C₂₄-alkyl groups, such as ahexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl ortetradecyl group; substituted or unsubstituted C₃-C₂₄-alkenyl groups,such as propenyl group; substituted or unsubstituted arylalkyl groups,such as a benzyl group; and substituted or unsubstituted aryl groups,such as a phenyl or naphthyl group. Suitable alkyl substituents includehalo (e.g. fluoro, chloro, bromo or iodo) groups, and alkoxy,cycloalkyl, substituted and unsubstituted, quaternary, amido, sulfone,sulfoxide, alkoxy and aryl groups. Suitable aryl and arylalkylsubstituents include fluoro, chloro, bromo, iodo, amino, ammonioalkyl,alkyl, alkoxy, hydroxy, alkoxy, sulfoxide and sulfone groups.

[0016] In one embodiment, at least 10% of the amino nitrogen atomswithin the polymer to be administered bear a hydrophobic substituent,such as a C₂-C₂₄-alkyl group. Preferably at least about 20% of the aminonitrogen atoms bear a hydrophobic substituent. In other embodiments, atleast about 40% of the amino nitrogen atoms can bear a hydrophobicsubstituent.

[0017] In general, poly(diallylamine) polymers are characterized bymonomers, or repeat units, comprising five-membered rings, monomerscomprising six-membered rings, or a combination thereof. In oneembodiment, the polymer to be administered is characterized by anammonium-bearing monomer of Formula I or of Formula II

[0018] or a combination thereof, wherein R¹ is a hydrophobicsubstituent, as described above, and R² is hydrogen, methyl, or ahydrophobic substituent. In a preferred embodiment, R¹ is selected fromamong the octyl, decyl and dodecyl groups and R² is methyl.

[0019] X⁻ is an anion, such as the conjugate base of a pharmaceuticallyacceptable acid. Such anions include chloride, citrate, tartrate,lactate, phosphate, hydrophosphate, methanesulfonate, acetate, formate,maleate, fumarate, malate, succinate, malonate, sulfate, hydrosulfate,L-glutamate, L-aspartate, pyruvate, mucate, benzoate, glucuronate,oxalate, ascorbate and acetylglycinate. In a preferred embodiment, X⁻ ischloride.

[0020] In another embodiment, the polymer to be administered ischaracterized by an amine-bearing monomeric unit of Formula III orFormula IV

[0021] or a combination thereof, wherein R is a hydrophobic substituentas previously described.

[0022] In a preferred embodiment, the polymer to be administeredcomprises one or more monomers of Formulas I-IV wherein at least 10%,preferably at least about 20%, of the amino nitrogen atoms bear aC₃-C₂₄-alkyl substituent. \Examples of particularly preferredC₃-C₂₄-alkyl groups include hexyl, heptyl, octyl, nonyl, decyl, undecyl,dodecyl, tridecyl and tetradecyl groups.

[0023] The polymer to be administered can be a copolymer comprising oneor more diallylamine monomers, such as one or more monomers of FormulasI, II, III, and IV, and at least one additional monomer. In oneembodiment, the additional monomer is sulfur dioxide. In polymerscomprising sulfur dioxide, the polymer backbone includes —SO₂— unitsbetween pairs of diallylamine monomers.

[0024] In a further embodiment, the invention provides a method forremoving bile acids from a patient comprising the step of administeringto the patient a therapeutically effective amount of a polymercharacterized by a diallylamine repeat unit wherein the amino nitrogenatom bears an ammonioalkyl substituent. The invention also includes theammonioalkyl-substituted polymers which are of use in this method.

[0025] The term “ammonioalkyl”, as used herein, refers to an alkyl groupwhich is substituted by a nitrogen atom bearing three additionalsubstituents. Thus, the nitrogen atom is an ammonium nitrogen atom whichbears an alkylene substituent, which links this atom to the diallylaminenitrogen atom, and three additional substituents selected from amonghydrogen, alkyl and arylalkyl. An ammonioalkyl group will furtherinclude a negatively charged counter ion, such as a conjugate base of apharmaceutically acceptable acid.

[0026] The diallylamine repeat unit can be, for example, of Formula I,Formula II, Formula III, or Formula IV, wherein at least one of thenitrogen substituents is an ammonioalkyl substituent. Suitableammonioalkyl substituents are of the general formula

[0027] wherein R⁴, R⁵ and R⁶ are each, independently, a hydrogen atom ora C₁-C₂₄ alkyl group; n is an integer from 2 to about 20, preferablyfrom 3 to about 6; and X⁻ is an anion, such as a conjugate base of apharmaceutically acceptable acid. Preferably, at least one of R⁴, R⁵ andR⁶ is a hydrophobic group such as a C₃-C₂₄-alkyl group. More preferably,at least one of R⁴, R⁵ and R⁶ is a C₆-C₂₄-alkyl group. Suitable examplesof ammonioalkyl groups include, but are not limited to,4-(dioctylmethylammonio)butyl; 3-(dodecyldimethylammonio)propyl;3-(octyldimethylammonio)propyl; 3-(decyldimethylammonio)propyl;5-(dodecyldimethylammonio)pentyl; 3-(cyclohexyldimethylammonio)propyl;3-(decyldimethylammonio)-2-hydroxypropyl; 3-(tridecylammonio)propyl;3-(docosyldimethylammonio)propyl; 4-(dodecyldimethylammonio)butyl;3-(octadecyldimethylammonio)propyl; 3-(hexyldimethylammonio)propyl;3-(methyldioctylammonio)propyl; 3-(didecylmethylammonio)propyl;3-(heptyldimethylammonio)propyl; 3-(dimethylnonylammonio)propyl;6-(dimethylundecylammonio)hexyl; 4-(heptyldimethylammonio)butyl;3-(dimethylundecylammonio)propyl; and3-(tetradecyldimethylammonio)propyl.

[0028] The polymer can be a homopolymer which comprises only a monomerselected from among Formulas I-IV, above, wherein the nitrogen atombears at least one ammonioalkyl substituent. The polymer can also be acopolymer which comprises a monomer of this type and at least oneadditional monomer. For example, the polymer can comprise a seconddiallylamine monomer wherein the nitrogen atom bears a substituentselected from among hydrogen, methyl, ethyl, hydrophobic groups andammonioalkyl groups.

[0029] The polymer can also comprise an additional monomer which is nota diallylamine. Suitable examples of additional polymers includesubstituted and unsubstituted acrylate, acrylamide, methacrylate,methacrylamide, allylamine, allyl alcohol, vinyl amine and vinylalcohol. For example, the additional monomer can be a substitutedacrylate or acrylamide which bears a hydrophobic group, such as aC₃-C₂₄-alkylacrylate or an N—C₃-C₂₄-alkylacrylamide. The additionalmonomer can also be a hydrophilic monomer, such asN-(2-hydroxyethyl)acrylamide or (3-hydroxypropyl)acrylate. Also includedare the multifunctional crosslinking co-monomers which are discussed indetail below.

[0030] The copolymers can have a wide range of compositions. Typically,the ammonioalkyl-substituted diallylamine monomer will constitute fromabout 10% to about 90% of the monomeric units composing the polymer.

[0031] The polymers of use in the present method can be linear orcrosslinked. The polymer can be crosslinked, for example, by theincorporation within the polymer of a multifunctional comonomer.Suitable multifunctional co-monomers include diacrylates, triacrylatesand tetraacrylates, dimethacrylates, diacrylamides, diallylacrylamideand di(methacrylamides). Specific examples include ethylene glycoldiacrylate, propylene glycol diacrylate, butylene glycol diacrylate,ethylene glycol dimethacrylate, butylene glycol dimethacrylate,methylene bis(methacrylamide), ethylene bis(acrylamide), ethylenebis(methacrylamide), ethylidene bis(acrylamide), ethylidenebis(methacrylamide), pentaerythritol tetraacrylate, trimethylolpropanetriacrylate, bisphenol A dimethacrylate, and bisphenol A diacrylate.Other suitable multifunctional monomers include polyvinylarenes, such asdivinylbenzene. The amount of crosslinking agent is typically between1.0% and 25% by weight relative to the weight of the polymer, preferablyfrom about 2.5% to about 20% by weight and more preferably from about 2%to about 12% by weight.

[0032] The polymer can also be crosslinked by bridging units which linkamino groups on adjacent polymer strands. Suitable bridging unitsinclude straight chain or branched, substituted or unsubstitutedalkylene groups, diacylalkylene groups, diacylarene groups and alkylenebis(carbamoyl) groups. Examples of suitable bridging units include—(CH₂)_(n)—, wherein n is an integer from about 2 to about 20;—CH₂—CH(OH)—CH₂—; —C(O)CH₂CH₂C(O)—;—CH₂—CH(OH)—O—(CH₂)_(n)—O—CH(OH)—CH₂—, wherein n is 2 to about 4;—C(O)—(C₆H₂(COOH)₂)—C(O)— and —C(O)NH(CH₂)_(p)NHC(O)—, wherein p is aninteger from about 2 to about 20.

[0033] Advantageously, crosslinking the polymers renders the polymersnon-adsorbable and stable in the patient. A “stable” polymercomposition, when administered in therapeutically effective amounts,does not dissolve or otherwise decompose to form potentially harmfulbyproducts, and remains substantially intact.

[0034] Polymers of use in the present method are, preferably, of amolecular weight which enables them to reach and remain in thegastrointestinal tract for a sufficient period of time to bind asignificant amount of one or more bile acids. The polymers should, thus,be of sufficiently high molecular weight to resist, partially orcompletely, absorption from the gastrointestinal tract into otherregions of the body. The resulting polymer/bile salt complex should thenbe excreted from the body. Suitable linar (non-crosslinked) polymershave molecular weights which range from about 2,000 Daltons to about500,000 Daltons, preferably from about 5,000 Daltons to about 150,000Daltons. Crosslinked polymers, however, are not generally chaacterizedby molecular weight. The crosslinked polymers discussed herein should besufficiently crosslinked to resist adsorption from the gastrointestinaltract.

[0035] The polymer network can be administered orally to a patient in adosage of about 1 mg/kg/day to about 10 g/kg/day; the particular dosagewill depend on the individual patient (e.g., the patient's weight andthe extent of bile salt removal required). The polymer can beadministered either in hydrated or dehydrated form, and can be flavoredor added to a food or drink, if desired, to enhance patient acceptance.Additional ingredients such as other bile acid sequestrants, drugs fortreating hypercholesterolemia, atherosclerosis or other relatedindications, or inert ingredients, such as artificial coloring agents,may be added as well.

[0036] Examples of suitable forms for administration include pills,tablets, capsules, and powders (i.e. for sprinkling on food). The pill,tablet, capsule or powder can be coated with a substance capable ofprotecting the composition from the gastric acid in the patient'sstomach for a period of time sufficient for the composition to passundisintegrated into the patient's small intestine. The polymer can beadministered alone or in combination with a pharmaceutically acceptablecarrier, diluent or excipient substance, such as a solid, liquid orsemi-solid material. Examples of suitable carriers, diluents andexcipients include lactose, dextrose, sucrose, sorbitol, mannitol,starches, gum acacia, alginates, tragacanth, gelatin, calcium silicate,cellulose and others known in the art.

[0037] Polymers of use in the present method can be prepared usingtechniques known in the art of polymer synthesis (see for example,Shalaby et al., ed., Water-Soluble Polymers, American Chemical Society,Washington D.C. (1991)). For example, the appropriate monomer can bepolymerized by methods known in the art, for example, via a free radicaladdition process. In this case the polymerization mixture includes afree-radical initiator, such as a free radical initiator selected fromamong those which are well known in the art of polymer chemistry.Suitable free-radical initiators include azobis(isobutyronitrile),azobis(4-cyanovaleric acid), azobis(amidinopropane) dihydrochloride,potassium persulfate, ammonium persulfate and potassium hydrogenpersulfate. The free radical initiator is preferably present in thereaction mixture in an amount ranging from about 0.1 mole percent toabout 5 mole percent relative to the monomer.

[0038] The polymer can be crosslinked, for example, by including amultifunctional co-monomer as the crosslinking agent in the reactionmixture. A multifunctional co-monomer can be incorporated into two ormore growing polymer chains, thereby crosslinking the chains. Suitablemultifunctional co-monomers include those discussed above. The amount ofcrosslinking agent added to the reaction mixture is, generally, between1.0% and 25% by weight relative to the combined weight of the polymerand the crosslinking agent, and preferably from about 2.5% to about 20%by weight.

[0039] The multifunctional co-monomer can also take the form of amultifunctional diallylamine, such as a bis(diallylamino)alkane or abis(diallylalkylammonio) alkane. Suitable monomers of this type include1,10-bis(diallylmethylammonio)decane dibromide and1,6-bis(diallylmethylammonio)hexane, each of which can be formed by thereaction of diallylmethylamine with the appropriate dibromoalkane.

[0040] The polymers to be administered can also be crosslinkedsubsequent to polymerization by reacting the polymer with one or morecrosslinking agents having two or more functional groups, such aselectrophilic groups, which react with amine groups to form a covalentbond. Crosslinking in this case can occur, for example, via nucleophilicattack of the polymer amino groups on the electrophilic groups. Thisresults in the formation of a bridging unit which links two or moreamino nitrogen atoms from different polymer strands. Suitablecrosslinking agents of this type include compounds having two or moregroups selected from among acyl chloride, epoxide, and alkyl-X, whereinX is a suitable leaving group, such as a halo, tosyl or mesyl group.Examples of such compounds include epichlorohydrin, succinyl dichloride,butanedioldiglycidyl ether, ethanedioldiglycidyl ether, pyromelliticdianhydride and dihaloalkanes. The crosslinking agent can also be anα,ω-alkylene diisocyanate, for example OCN(CH₂)_(p)NCO, wherein p is aninteger from about 2 to about 20. The polymer can be reacted with anamount of crosslinking agent equal from about 0.5 and 20 mole percentrelative to the amino groups within the polymer, depending upon theextent of crosslinking desired.

[0041] A polymer comprising alkylated amino groups can be formed byreacting a preformed polymer with a suitable alkylating agent, or bypolymerizing an alkylated monomer. Suitable alkylated monomers can beprepared by reacting diallylamine or a diallylamine derivative, such asdiallylmethylamine, with an alkylating agent. As used herein, the term“alkylating agent” refers to a compound which reacts with an amino groupto form a nitrogen-carbon bond, thereby adding an alkyl or alkylderivative substituent to the nitrogen atom. Suitable alkylating agentsare compounds comprising an alkyl group or alkyl derivative which isbonded to a leaving group, such as a halo, tosylate, mesylate or epoxygroup. Examples of preferred alkylating agents include C₁-C₂₄-alkylhalides, for example, n-butyl halides, n-hexyl halides, n-decyl halides,and n-octadecyl halides; C₂-C₂₄-dihaloalkanes, for example,1,10-dihalodecanes; C₁-C₂₄-hydroxyalkyl halides, for example,11-halo-1-undecanols; C₁-C₂₄-arylalkyl halides, for example, benzylhalide; C₂-C₂₄-alkylepoxy ammonium salts, for example,glycidylpropyl-trimethylammonium salts; and C₂-C₂₄-epoxyalkylamides, forexample, N-(2,3-epoxypropyl)butyramide or N-(2,3-epoxypropyl)hexanamide.Preferred alkylating agents include halodecane, and halododecane, wherein each case “halo” represents a chloro, bromo or iodo substituent.

[0042] Diallylamine polymers having amino groups which bear quaternaryammonium-substituted alkyl groups can be prepared using alkylatingagents such as (X-alkyl)ammonium salts, wherein X represents a suitableleaving group, as described above. These compounds can be prepared bythe reaction of an appropriate dihaloalkane, such as abromochloroalkane, with a tertiary amine. Suitable alkylating agents ofthis type include the following:

[0043] (4-bromobutyl)dioctylmethylammonium bromide;

[0044] (3-bromopropyl)dodecyldimethylammonium bromide;

[0045] (3-chloropropyl)dodecyldimethylammonium bromide);

[0046] (3-bromopropyl)octyldimethylammonium bromide;

[0047] (3-chloropropyl)octyldimethylammonium bromide;

[0048] (3-iodobutyl)dioctylmethylammonium bromide;

[0049] (2,3-epoxypropyl)decyldimethylammonium bromide;

[0050] (3-chloropropyl)decyldimethylammonium bromide;

[0051] (5-tosylpentyl)dodecyldimethylammonium bromide;

[0052] (6-bromohexyl)octyldimethylammonium bromide;

[0053] (12-bromododecyl)decyldimethylammonium bromide;

[0054] (3-bromopropyl)tridecylammonium bromide;

[0055] (3-bromopropyl)docosyldimethylammonium bromide;

[0056] (6-bromohexyl)docosyldimethylammonium bromide;

[0057] (4-chlorobutyl)dodecyldimethylammonium bromide;

[0058] (3-chloropropyl)octadecyldimethylammonium bromide;

[0059] (3-chloropropyl)hexyldimethylammonium bromide;

[0060] (3-chloropropyl)methyldioctylammonium bromide;

[0061] (3-chloropropyl)methyldidecylammonium bromide;

[0062] (3-chloropropyl)cyclohexyldimethylammonium bromide;

[0063] (3-bromopropyl)heptyldimethylammonium bromide;

[0064] (3-bromopropyl)dimethylnonylammonium bromide;

[0065] (6-bromohexyl)dimethylundecylammonium bromide;

[0066] (4-chlorobutyl)heptyldimethylammonium bromide;

[0067] (3-chloropropyl)dimethylundecylammonium bromide; and

[0068] (3-chloropropyl)tetradecyldimethylammonium bromide.

[0069] Each of the alkylating agents described above can also exist andbe used as a salt in combination with an anion other than bromide. Forexample, these and similar alkylating agents can be prepared and used assalts with a wide range of anions, including chloride, iodide, acetate,p-toluenesulfonate and methanesulfonate.

[0070] When the hydrophobic groups are added to the polymer by way of analkylating agent as described above, the extent of alkylation can bedetermined by methods which are well known in the chemical arts. Theincrease in polymer mass due to alkylation provides one measure of theextent of alkylation. For example, in a reaction betweenpoly(diallylmethylamine) and 1-bromodecane, a product/starting materialmass ratio of about 3.0, 2.0 and 1.5 represent approximately 100%, 50%and 25% alkylation, respectively. The degree of alkylation can also bedetermined by elemental analysis of the product polymer. In this case,the carbon/nitrogen (C/N) mass ratio is a direct measure of the degreeof alkylation. For example, the reaction of poly(diallylmethylamine)with 1-bromodecane yields a product with a higher C/N mass ratio thanthat of the starting polymer. Product C/N mass ratios of about 6, 8.2,10.6 and 14.6 represent, approximately, 0%, 25%, 50% and 100%alkylation, respectively.

[0071] The invention will now be further and specifically described bythe following examples.

EXAMPLES Example 1 Synthesis of Diallylmethyldodecylammonium Bromide

[0072] To a 2 L Morton flask was added diallylmethylamine (100 g),1-bromododecane (249 g), and tetrahydrofuran (750 mL). The mixture washeated to 65° C. for 44 h, and then allowed to cool to room temperature.The solvent was removed by rotary vacuum evaporation to leave twolayers. Diethylether (500 mL) was added and the mixture was stirred for1 hr. The mixture was allowed to settle and the top layer was decantedand discarded. Additional diethylether (500 mL) was added. The mixturewas stirred for 24 h, and the top layer was again decanted anddiscarded. The remaining oil was dried in a vacuum oven at 65° C. for 4days to yield 67 g of product.

Example 2 Synthesis of 1,10-Bis(diallylmethylammonio)decane Dibromide

[0073] To a 1 L Morton flask was added diallylmethylamine (86.1 g),1,10-dibromodecane (112 g), and methanol (100 mL). The mixture washeated to 65° C. for 24 h, and then allowed to cool to room temperature.The solvent was removed by rotary vacuum evaporation. Diethylether (400mL) was added and the mixture was stirred for 1 hr. The mixture wasallowed to settle and the top layer was decanted and discarded. Theremaining oil was dried by rotary vacuum evaporation to yield 215 g ofproduct.

Example 3 Synthesis of 1,6-Bis(diallylmethylammonio)hexane Dibromide

[0074] To a 1 L Morton flask was added diallylmethylamine (74.6 g),1,6-dibromohexane (77 g), and methanol (100 mL). The mixture was heatedto 65° C. for 17 h, and then allowed to cool to room temperature.Diethylether (300 mL) was added and the mixture was stirred for 1 hr.The solid was collected by filtration and resuspended in diethylether(200 mL). The mixture was stirred for 1 hr, and the solid againcollected by filtration. The solid was then dried in a vacuum oven at50° C. for 3 days to yield 136 g of product.

Example 4 Synthesis of Poly[1,10-bis(diallylmethylammonio)-decaneDibromide]

[0075] To a 250-mL, round bottom flask was added1,10-bis(diallylmethylammonio) decane dibromide (20 g) and water (40 g).Azobisisobutyramidine dihydrochloride (0.5 mL of a 50% aqueous solution)was added and nitrogen was bubbled through the mixture for 1 hr. Themixture was then heated to 60° C. with stirring for 4 hr, at which timeadditional azobisisobutyramidine dihydrochloride (0.5 mL of a 50%aqueous solution) was added.

[0076] After 18 hr the solution was allowed to cool to room temperature.The resulting gel was removed and ground in a blender with water (500mL). The solid was collected by centrifugation and resuspended inmethanol (500 mL). After stirring for 1 hr, the solid was collected byfiltration and resuspended in aqueous NaCl (500 mL of 1.5 M solution).After again stirring for 1 hr, the solid was collected by filtration.The aqueous NaCl rinse was repeated twice more, and the solid was rinsedwith water until the conductivity of the rinse reached 0.3 mS/cm. Thesolid was dried in a forced air at 60° C. to yield 10.0 g of product.

Example 5 Synthesis of Copoly[1,10-bis(diallylmethylammonio)decaneDibromide/Diallylmethyldodecylammonium Bromide]

[0077] To a 500-mL round bottom flask was added1,10-bis(diallylmethylammonio) decane dibromide (21.1 g),diallylmethyldodecylammonium bromide (21.1 g), and water (52 g).Azobisisobutyramidine dihydrochloride (1 mL of a 50% aqueous solution)was added and nitrogen was bubbled through the mixture for 1 hr. Themixture was then heated to 60° C. with stirring for 18 hr. The resultinggel was allowed to cool to room temperature. The gel was removed andground in a blender with water (250 mL). The solid was collected byfiltration and resuspended in methanol (250 mL). The solid was collectedby filtration and resuspended in methanol (250 mL). After stirring for 1hr, the solid was collected by filtration and resuspended in aqueousNaCl (250 mL of 1.5 M solution). After again stirring for 1 hr, thesolid was collected by filtration. The aqueous NaCl rinse was repeatedtwice more, and the solid was rinsed with water until the conductivityof the rinse reached 0.08 mS/cm. The solid was dried in a forced-airoven at 60° C. to yield 17.6 g of product.

Example 6 Synthesis of Epichlorohydrin CrosslinkedPoly(diallylmethylamine)

[0078] A crosslinked gel of N-methyl-N; N-diallylamine polymer wasprepared by reacting the corresponding linear soluble polymer withepichlorohydrin. The starting material, poly(diallylmethylamine) wasobtained in the form of its hydrochloride salt from Nitto Boseki Co. Thepolymer was obtained as a 60% aqueous solution (PAS-M-1, Lot # 51017).The chemical process to obtain insoluble gels of this polymer involvedpartial neutralization of the amine hydrochloride polymer with a basefollowed by treatment with a predetermined amount of epichlorohydrin atroom temperature. Experimental details to obtain a typical crosslinkedgel of poly(diallylmethylamine hydrochloride) are given below.

[0079] 83 g of the polymer solution was diluted with 170 mL deionizedwater. While stirring, 6.8 g NaOH was added to the polymer solution. Thereaction mixture was allowed to stir until all NaOH had dissolved. Whenthe temperature of the solution had dropped to below 30° C.,epichlorohydrin (1.2 mL) was added and stirring continued. The reactionmedium slowly became viscous and after about 80 minutes, had gelled andthe stirring was stopped. The polymer gel was left at room temperaturefor an additional 60 hr. The polymer slab was broken into smaller piecesand dispersed in 400 mL deionized water. The resulting suspension wasstirred for 2 hr and then filtered. The swollen polymer particles wereresuspended in 600 mL deionized water, stirred for 45 minutes andcollected by filtration. The process was repeated with 800 mL water and1 hr stirring. After filtration, the filtrate showed a conductivity of 4mS/cm. The filtered polymer (swollen gel) was dried in a forced air ovenat 60° C. to yield 42 g of product.

Example 7 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromodecane

[0080] 25 g of the ground polymer (Example 6) taken in a 1 liter3-necked round bottom flask was suspended in 250 mL deionized water. Thepolymer swelled significantly and was stirred with a mechanical stirrer.To this swollen gel was added 100 g 1-bromodecane dissolved in 250 mLethanol and the reaction mixture was stirred for 10 minutes.Subsequently, 5 g of 50% aqueous sodium hydroxide was added and thereaction mixture was stirred at room temperature for 40 minutes followedby heating to 75° C. for 1 hr. 2 g NaOH solution was then added followedby additional 2 g of NaOH solution after another 1.5 hr (the baseaddition was such as to maintain the pH between 10 and 12). The reactionmixture was stirred at 75° C. for an additional 18 hours, after whichtime heating was discontinued. After cooling to 30° C., 5 mLconcentrated HCl was added and stirring was continued for 30 minutes.The pH of the medium dropped to 1.8. The polymer was filtered and washedwith 500 mL deionized water followed by 500 mL methanol. Polymerparticles were suspended in 600 mL methanol and stirred for 40 minutes.After removing the solvent by filtration, the polymer was suspended in500 mL of 2 M NaCl solution and stirred for 40 minutes. The polymer wasfiltered and this process of NaCl treatment was repeated two more times.The filtered polymer cake was washed with 500 mL deionized water andsuspended in 500 mL deionized water. After stirring for 30 minutes thepolymer was filtered and resuspended in 700 mL deionized water andstirred for 30 minutes. Concentrated HCl (2 mL) was added to thesuspension and the mixture was stirred for 15 minutes. The pH of thesuspension was found to be 2.25. After stirring for an additional 20minutes, the polymer was filtered and dried at 60° C. in a forced airoven, yielding 54.6 g of the alkylated polymer as a light yellow solid.The polymer was ground and passed through a 140 mesh sieve.

Example 8 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromododecane

[0081] 10 g of the ground polymer (Example 6) was suspended in 100 mLdeionized water in a 500 mL 3-necked round-bottomed flask. The polymerswelled significantly and was stirred with a mechanical stirrer. To thisswollen gel, 28 g 1-bromodecane dissolved in 100 mL ethanol was addedand the reaction mixture was stirred for 10 minutes. 2 g of 50% aqueoussodium hydroxide was then added and the reaction mixture was stirred atroom temperature for 40 minutes, followed by heating to 75° C. for 1 hr.1 g NaOH solution was then added followed by an additional 1 g of NaOHsolution after another 1.5 hr (the base addition was such as to maintainthe pH between 10 and 12). The reaction mixture was stirred at 75° C.for an additional 18 h after which time the heating discontinued. Aftercooling to 30° C., concentrated HCl (2 mL) was added and the mixture wasstirred for 30 minutes. The polymer was filtered and washed with 500 mLdeionized water followed by 500 mL methanol. Polymer particles weresuspended in 300 mL methanol and stirred for 40 minutes. After removingthe solvent by filtration, the polymer was suspended in 500 mL 2M NaClsolution and stirred for 40 minutes. It was filtered and this process ofNaCl treatment was repeated two more times. The filtered polymer cakewas washed with 500 mL deionized water and suspended in 500 mL deionizedwater. After stirring for 30 minutes the polymer was filtered andresuspended in 500 mL deionized water and stirred for 30 minutes.Concentrated HCl (2 mL) was added to the suspension and the mixture wasstirred for 15 minutes. The pH of the suspension was found to be 2.2.After stirring for an additional 20 minutes, the polymer was filteredand dried at 60° C. in a forced air oven, yielding 18 g of the alkylatedpolymer as a pale white solid. The polymer was ground and passed througha 140 mesh sieve.

Example 9 Preparation of (3-chloropropyl)-dodecyldimethylammoniumBromide

[0082] A two-liter, 3-necked, round-bottomed flask equipped with an aircondenser and a magnetic stirring plate was charged withN,N-dimethyldodecylamine (297.24 grams, 1.40 moles),1-bromo-3-chloropropane (220.44 grams, 1.40 moles) and methanol (250mL). Reaction was maintained at 65° C. for 24 hours. Methanol wasremoved by rotary evaporation under reduced pressure to yield a brownsludge. To the sludge was added methyl-tert-butylether (2 liters)causing a white solid to form. The mixture was stirred for two hours anda semi-crystalline, white particulate was collected by vacuumfiltration. The particulate was dried in a vacuum oven at 35° C. for 24hours. Yield 228.2 grams (0.61 moles, 44%).

[0083] (4-Chlorobutyl)dodecyldimethylammonium bromide and(6-chlorohexyl) dodecyldimethylammonium bromide can be prepared by asimilar process using the appropriate bromochloroalkane anddodecyldimethylamine.

Example 10 Alkylation of Crosslinked Poly(diallylmethylamine) with(3-chloropropyl)dimethyldodecylammonium Bromide

[0084] A mixture of 11 g crosslinked polymer gel (Example 6) and 74 g(3-chloropropyl)-dimethyldodecylammonium bromide was dispersed in 250 mLdeionized water and heated to 75° C. with stirring. After stirring at75° C. for 15 minutes, 2 g of a 50% aqueous NaOH solution was added tothe reaction mixture. After 2 hr, 1 g of NaOH solution was addedfollowed by an additional 1 g after another 1 hr and the mixture wasstirred at 75° C. for 23 hr. The reaction mixture was then allowed tocool. After cooling to 30° C., 3 mL concentrated HCl was added and themixture was stirred for 30 minutes. The polymer was filtered and washedwith 200 mL methanol. The filtered polymer particles were dispersed in400 mL methanol and stirred for 45 minutes and filtered. This processwas repeated one more time, then the filtered polymer was suspended in500 mL 2M NaCl solution, stirred for 45 minutes and filtered. Thisprocess of NaCl treatment was repeated twice and the filtered polymerwas suspended in 500 mL deionized water. The mixture was stirred for 45minutes, filtered, resuspended in 400 mL deionized water and stirred foran additional 40 minutes. To this suspension, 1 mL concentrated HCl wasadded and the mixture was stirred for 20 minutes. The polymer wasfiltered and dried in a forced air oven at 60° C., yielding 29 g ofalkylated polymer as a light yellow solid which was ground and passedthrough a 140 mesh sieve.

Example 11 Alkylation of Crosslinked Poly(diallylmethylamine) with(4-chlorobutyl)dimethyldodecylammonium Bromide

[0085] A mixture of 10 g 3% crosslinked polymer gel (Example 6) and 76 g(4-chlorobutyl)dimethyldodecyl-ammonium bromide was dispersed in 250 mLdeionized water and heated to 70° C. with stirring for 15 minutes. 2 g50% aqueous solution of NaOH was then added to the reaction mixture.After 2 hr, 1 g NaOH solution was added followed by additional 1 g afteranother 2 hr. The reaction mixture was then stirred at 70° C. for 20hours. 1 g NaOH was then added and the reaction mixture was kept at 70°C. After 20 hr heating, 1 g NaOH solution was added and the reactionmixture was kept at 70° C. with stirring for 2 hr. After cooling to 30°C., 2 mL of concentrated HCl was added and the mixture was stirred for20 minutes. The polymer was filtered and washed successively with 200 mLdeionized water and 200 mL methanol. The filtered polymer particles werethen dispersed in 500 mL methanol, stirred for 30 minutes, and filtered.This process was repeated an additional time and the filtered polymerwas suspended in 400 mL 2M NaCl solution, stirred for 45 minutes andfiltered. After repeating NaCl treatment twice, the filtered polymer wassuspended in 400 mL deionized water. The mixture was stirred for 30minutes, filtered, resuspended in 400 mL deionized water and stirred foran additional 40 minutes. To this polymer suspension, 1 mL concentrated.HCl was added and the mixture was stirred for 20 minutes. The polymerwas then filtered and dried in a forced air oven at 60° C., yielding 27g alkylated polymer as a light yellow solid which was ground and passedthrough a 140 mesh sieve.

Example 12 Alkylation of Crosslinked Poly(diallylmethylamine) with(6-chlorohexyl)-dimethyloctylammonium Bromide

[0086] A mixture of 10 g 3% crosslinked polymer gel (Example 6) and 71 g(6-chlorohexyl)dimethyldodecyl-ammonium bromide was dispersed in 200 mLdeionized water and heated to 75° C. with stirring for 15 minutes. 2 g50% aqueous solution of NaOH was then added to the reaction mixture.After 3 hr, 1 g NaOH solution was added. After 2.5 hr an additional 1 gof NaOH solution was added and the reaction mixture was stirred at 75°C. for 22 hr. 0.5 g NaOH was then added and heating was continued for anadditional 2 hr. After cooling to 30° C., 2 mL concentrated HCl wasadded and the mixture was stirred for 15 minutes. The polymer was thenfiltered and washed successively with 200 mL deionized water and 200 mLmethanol. The filtered polymer particles were then dispersed in 500 mLmethanol, stirred for 30 minutes and filtered. This process was repeatedtwo times, then the filtered polymer was suspended in 400 mL 2M NaClsolution, stirred for 45 minutes and filtered. After repeating the NaCltreatment twice, the filtered polymer was suspended in 400 mL deionizedwater. The mixture was stirred for 30 minutes, filtered, and resuspendedin 400 mL deionized water and stirred for an additional 40 minutes. Tothis polymer suspension was added 1 mL concentrated HCl and the mixturewas stirred for 20 minutes. The polymer was filtered and dried in aforced air oven at 60° C., yielding 25 g alkylated polymer as a whitesolid, which was ground and passed through a 140 mesh sieve.

Example 13 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromodecane

[0087] This example illustrates alkylation of the 4.5% crosslinkedpoly(diallylmethylamine) with different amounts of 1-bromodecane toobtain quaternized polyamines bearing varying amounts of hydrophobicgroups. For this purpose, the polymer was treated with varying molefractions of 1-bromodecane (1.0, 0.75, 0.50, 0.25 and 0.10). Table 1summarizes amounts of 1-bromoalkane used to obtain polymers of varyingdegree of alkylation and the yield of alkylated polymer per gram of the4.5% crosslinked poly (diallylmethylamine) (Example 2). This g/g yieldis a measure of the degree of alkylation of the polymer.

[0088] 10 g of the 4.5% crosslinked poly(diallylmethyl-amine) wassuspended in 150 mL deionized water. While stirring, 2 g 50% aqueousNaOH solution was added to the polymer and the suspension was stirredfor 15 minutes. At this time an ethanol solution of 1-bromodecane (2.5mL ethanol/g 1-bromodecane) was added and the reaction mixture washeated to 75° C. with stirring. After 2 hr, 1 g NaOH was added, followedby an additional 1 g of NaOH after another 2 hr. The reaction mixturewas stirred at 75° C for 18 hours and was then allowed to cool. Aftercooling to 30° C., 2 mL concentrated HCl was added and the mixture wasstirred for 15 minutes. The polymer was filtered and washed with 200 mLdeionized water and 200 mL methanol for 30 minutes and filtered. Thisprocess was repeated twice and the filtered polymer was suspended in 400mL of 2M NaCl solution, stirred for 45 minutes and filtered. Afterrepeating the NaCl treatment twice, the filtered polymer was suspendedin 400 mL deionized water. The mixture was stirred for an additional 30minutes, filtered, resuspended in 400 mL deionized water and stirred foran additional 40 minutes. To this polymer suspension was added 1 mLconcentrated HCl and the mixture was stirred for 20 minutes. The polymerwas filtered, dried in a forced air oven at 60° C., ground and passedthrough a 140 mesh sieve. Yield of the polymers for different amounts ofthe 1-bromodecane used are summarized in Table 1. The calculation of %alkylation assumed protonation of 50% of the amino nitrogen atoms. TABLE1 Results of the alkylation of 4.5% crosslinked poly(diallylmethylamine) with varying amounts of 1-bromodecane (C₁₀H₂₁Br)(“ratio” = ratio of 1-bromodecane to polymer amino groups (mole/mole)).product/ Polymer C₁₀H₂₁Br product starting Used used yield polymer (g)(g) Ratio (g) (g/g) % alkylation 10.0 17.0 1.0 17 1.7 35 10.0 12.5 0.7516.8 1.68 34 10.0 8.0 0.50 14.3 1.43 22 10.0 4.25 0.25 11.8 1.18 9 10.01.70 0.10 10.6 1.06 3

Example 14 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromotetradecane

[0089] 10 g of 4.5% crosslinked polydiallylmethylamine (Example 6) wassuspended in 100 mL in a 500 mL 3-necked round-bottomed flask ofdeionized water. The polymer swelled significantly and was stirred witha mechanical stirrer. To this swollen gel, was added 32 g1-bromotetradecane dissolved in 100 mL ethanol, and the reaction mixturewas stirred for 10 minutes. 2 g 50% aqueous sodium hydroxide was thenadded and the reaction mixture was stirred at room temperature for 40minutes followed by heating to 75° C. for 1 hr. 1 g NaOH solution wasthen added followed by an additional 1 g of NaOH solution after another1.5 hr (the base addition was such as to maintain the pH between 10 to12). The reaction mixture was stirred at 75° C. for an additional 18hours after which time the heating was discontinued. After cooling to30° C., 2 mL concentrated HCl was added and the mixture was stirred for30 minutes. The polymer was filtered and washed with 500 mL deionizedwater followed by 500 mL methanol. Polymer particles were suspended in300 mL methanol and stirred for 40 minutes. After removing the solventby filtration, the polymer was suspended in 500 mL of 2M NaCl solutionand stirred for an additional 40 minutes. The polymer was filtered andthis process of NaCl treatment was repeated twice. The filtered polymercake was then washed with 500 mL deionized water and suspended in 500 mLdeionized water. After stirring for 30 minutes the polymer was filteredand resuspended in 500 mL deionized water and the suspension was stirredfor 30 minutes. 1 mL concentrated HCl was then added to the suspension,which was stirred for another 55 minutes. The polymer was then filteredand dried at 60° C. in a forced air oven, yielding 22 g of the alkylatedpolymer. The polymer was ground and passed through a 140 mesh sieve.

Example 15 Alkylation of Crosslinked Poly(diallylmethylamine) with1-Bromooctane

[0090] 10 g of 4.5% crosslinked poly(diallylmethylamine) (Example 7) wassuspended in 100 mL in a 500 mL 3-necked round bottom flask of deionizedwater. The polymer swelled significantly and was stirred with amechanical stirrer. To this swollen gel, was added 23 g 1-bromooctanedissolved in 100 mL ethanol and the reaction mixture was stirred for 10minutes. 2 g of 50% aqueous sodium hydroxide was then added and thereaction mixture was stirred at room temperature for 40 minutes,followed by heating to 75° C. for 1 hr. 1 g NaOH solution was thenadded, followed by an additional 1 g of NaOH solution after another 1.5hr. The reaction mixture was allowed to stir at 75° C. for an additional18 hours after which time the heating was discontinued. After cooling to30° C., 2 mL concentrated HCl was added and stirring was continued for30 minutes. The polymer was filtered and washed with 500 mL deionizedwater followed by 500 mL methanol. Polymer particles were suspended in300 mL methanol and stirred for 40 minutes. After removing the solventby filtration, the polymer was suspended in 500 mL 2M NaCl solution andthe suspension was stirred for 40 minutes. The polymer was filtered andthis process of NaCl treatment was repeated twice. The filtered polymercake was washed with 500 mL deionized water and suspended in 500 mLdeionized water. After stirring for 30 minutes the polymer was filtered,resuspended in 500 mL deionized water, and stirred for 30 minutes. 1 mLconcentrated HCl was added to the suspension and stirred for 35 minutes.The polymer was then filtered and dried at 60° C. in a forced air oven,yielding 15.8 g of the alkylated polymer. The polymer was ground andpassed through a 140 mesh sieve.

Example 16 Alkylation of Crosslinked Poly(diallylmethylamine) with1-Bromohexane

[0091] 10 g of 4.5% crosslinked poly(diallylmethylamine) (Example 6)taken in a 500 mL 3-necked round bottom flask was suspended in 100 mLdeionized water. The polymer swelled significantly and was stirred witha mechanical stirrer. To this swollen gel was added, 19 g 1-bromodecanedissolved in 100 mL ethanol was added and the reaction mixture wasstirred for 10 minutes. 2 g of 50% aqueous sodium hydroxide was thenadded and the reaction mixture was stirred at room temperature for 40minutes, followed by heating to 75° C. for 1 hr. 1 g NaOH solution wasthen added followed by an additional 1 g of NaOH solution after another1.5 hr. The reaction mixture was stirred at 75° C. for an additional 18hours after which time the heating was discontinued. After cooling to30° C., 2 mL concentrated HCl was added and the mixture was stirred for30 minutes. The pH of the medium at this point was 2.0. The polymer wasfiltered and washed with 500 mL deionized water followed by 500 mLmethanol. The polymer particles were suspended in 300 mL methanol andstirred for 40 minutes. After removing the solvent by filtration, thepolymer was suspended in 500 mL of 2 M NaCl solution and the suspensionwas stirred for 40 minutes. The polymer was filtered and this process ofNaCl treatment was repeated twice. The filtered polymer cake was washedwith 500 mL deionized water and suspended in 500 mL deionized water.After stirring for 30 minutes, the polymer was filtered, resuspended in500 mL deionized water and stirred for 30 minutes. 1 mL concentrated HClwas added to the suspension, which was stirred for 35 minutes. Thepolymer was then filtered and dried at 60° C. in a forced air oven,yielding 13.7 g of the alkylated polymer. The polymer was ground andpassed through a 140 mesh sieve.

Example 17 Synthesis of Quaternized N-alkyl diallylmethylammonium Salts

[0092] Synthesis of N-decyldiallylmethylammonium bromide.

[0093] Diallylmethylamine (33.3 g) and 1-bromodecane (66.6 g) weredissolved in 100 mL methanol and the reaction mixture was stirred at 65°C. for 48 hours. After cooling to room temperature, the methanol wasremoved under reduced pressure. The residual viscous oil wasprecipitated into 800 mL dry ether with rapid stirring. The ether layerwas decanted and the residue was again treated with 500 mL dry ether.After stirring for 15 minutes the solvent was removed and the oilyresidue was dried under vacuum at 35° C. for 48 hours, yielding 78 g ofthe product.

[0094] Synthesis of N-(N,N-dimethyl-N-dodecylammonio)propyldiallylmethylammonium Chloride Bromide

[0095] A mixture of 22 g diallylmethylamine and 74 g3-chloropropyldodecyldimethylammonium bromide were dissolved in 100 mLmethanol and the reaction mixture was stirred at 65° C. for 48 hours.The progress of the reaction was monitored by the disappearance of thedialllymethylamine by thin layer chromatography (TLC). After cooling toroom temperature, the solvent was removed under reduced pressure. Theresidual viscous oil was precipitated into 800 mL dry ether with rapidstirring. The ether layer was decanted and the residue was again treatedwith 500 mL dry ether. After stirring for 15 minutes the solvent wasremoved and the oily residue was dried under vacuum at 35° C. for 48hours, yielding 70 g of the product.

[0096] Synthesis of N-(N,N-dimethyl-N-dodecylammonio)butyl-diallylmethylammonium Chloride bromide.

[0097] A mixture of 22 g diallylmethylamine and 75 g4-chlorobutyldimethyldodecylammonium bromide were dissolved in 100 mLmethanol and the reaction mixture was stirred at 65° C. for 48 hours.The progress of the reaction was monitored by the disappearance of thediallylmethylamine by thin layer chromatography (TLC). After cooling toroom temperature, the solvent was removed under reduced pressure. Theresidual viscous oil was precipitated into 800 mL dry ether with rapidstirring. The ether layer was decanted and the residue was again treatedwith 500 mL dry ether. After stirring for 15 minutes the solvent wasremoved and the oily residue was dried under vacuum at 35° C. for 48hours, yielding 65 g of the product.

[0098] Synthesis of Poly(N-decyldiallylmethylammonium bromide)Crosslinked with Methylenebis(acrylamide)

[0099] 25 g N-decyldiallylmethylammonium bromide, 3 gN,N-methylenebisacrylamide and 300 mg2,2′-azobis(2-amidinopropane)dihydrochloride were dissolved in 100 mLdeionized water. The solution was bubbled with a slow stream of nitrogenfor 30 minutes then heated to 70° C. with stirring. After 2 hr, thereaction mixture turned cloudy with formation of a suspension. Themixture was kept at 70° C. for a period of 18 hours and then allowed tocool. The suspension was centrifuged. The residue dispersed in 200 mLdeionized water, stirred for 30 minutes and centrifuged. After removalof the supernatant, the residue was suspended in 200 mL methanol,stirred for 30 minutes and centrifuged. The residue was suspended in 300mL methanol and the suspension was refluxed for 1 hr. After cooling toroom temperature, the suspension was filtered and the white solid wasdried at 60° C. for 24 hr to yield 10 g of the polymer. The polymer wasground and passed through 140 mesh sieve.

Example 19 Synthesis of Crosslinked Poly(diallylammoniumChloride-Co-Sulfur Dioxide) Copolymer

[0100] 111 g of a 20% solution of copoly(diallylmethyl-ammoniumchloride-co-sulfur dioxide) (PAS-92, obtained from Nitto Boseki Co.,Japan) was treated with 2.2 g solid NaOH with stirring. The solutionturned cloudy and phase separation occurred. The bottom viscous layerwas separated from the top layer and the former was diluted with 20 mLwater. To this solution, 0.6 mL epichlorohydrin was added and thereaction mixture was allowed to stir for 2 hr. The reaction mediumslowly became increasingly viscous and was left at room temperature for48 hours, during which period it turned into a gel. The resultingpolymer gel was broken into smaller pieces and was dispersed in 1 literdeionized water. The suspension was stirred for 1 hr and filtered. Theswollen polymer particles were resuspended in 800 mL deionized water andstirred for 1.5 hr. The polymer particles were then filtered and driedin a forced air oven at 60° C. to yield 16 g of polymer. The driedpolymer was ground and passed through a 10 mesh sieve.

Example 20 Alkylation of 6% CrosslinkedCopoly(diallylmethylamine-co-sulfur Dioxide) with 1-bromodecane

[0101] The polymer (5 g) of Example 20 was placed in a 500 mL 3-neckedround bottom flask and suspended in 100 mL deionized water. The polymerswelled significantly and was stirred with a mechanical stirrer. To thisswollen gel, a solution of 18 g 1-bromodecane in 100 mL ethanol wasadded and the reaction mixture stirred for 10 minutes. Subsequently, 2 g50% aqueous sodium hydroxide was added and the reaction mixture wasstirred at room temperature for 30 minutes followed by heating to 75° C.After 1 hr, 0.5 g NaOH solution was added followed by an additional 0.5g of NaOH solution after another 1.5 hr. The reaction mixture wasallowed to stir at 75° C. for an additional 18 hr after which time theheating was discontinued. After cooling to 30° C., 2 mL concentrated HClwas added and the mixture was stirred for 30 minutes. The pH of themedium dropped to 1.2. The polymer was filtered off and washed with 500mL deionized water and 500 mL methanol. Polymer particles were suspendedin 300 mL methanol and stirred for 40 minutes. After removing thesolvent by filtration, the polymer was suspended in 500 mL 2M NaClsolution and stirred for 40 minutes. The suspension was filtered and theNaCl treatment was repeated two more times. The filtered polymer cakewas washed with 500 mL deionized water and suspended in 500 mL deionizedwater. After stirring for 30 minutes it was filtered and resuspended in500 mL deionized water and stirred for 30 minutes. 1 mL of concentratedHCl was added to the suspension and the suspension was stirred for 35minutes. The polymer was then filtered and dried at 60° C. in a forcedair oven, yielding 9.1 g of the alkylated polymer. The polymer wasground and passed through a 140 mesh sieve.

Example 21 Alkylation of Crosslinked Copoly(diallylmethylamine-co-sulfurdioxide) with (3-chloropropyl)-Dimethyldodecylammonium Bromide

[0102] To a mixture of 5 g of the polymer of Example 20 and 30 g(3-chloropropyl)dimethyldodecylammonium bromide in a 500 mL 3-neckedround bottom flask was added 150 mL deionized water. The resultingmixture was stirred with a mechanical stirrer. 2 g of 50% aqueous sodiumhydroxide was added and the reaction mixture was stirred at roomtemperature for 30 minutes, followed by heating to 75° C. for 1 hr. NaOHsolution (0.5 g) was added, followed by an additional 0.5 g of NaOHsolution after another 1.5 hr. The reaction mixture was allowed to stirat 75° C. for an additional 18 hr after which time the heating wasdiscontinued. After cooling to 30° C., 2 mL concentrated HCl was addedand the mixture was stirred for 30 minutes. The pH of the medium droppedto 2.8. The polymer was filtered off and washed with 500 mL deionizedwater and 500 mL methanol. Polymer particles were then suspended in 300mL methanol and the suspension was stirred for 40 minutes. The polymerwas isolated by filtration and then suspended in 500 mL 2M NaClsolution. The suspension was stirred for 40 minutes. The polymer wasfiltered off and this NaCl treatment was repeated two more times. Thefiltered polymer cake was washed with 500 mL deionized water and thensuspended in 500 mL deionized water. After stirring for 30 minutes thepolymer was filtered off and resuspended in 500 mL deionized water. Thesuspension was stirred for 30 minutes. 1 mL concentrated HCl was addedto the suspension and the suspension was stirred for 35 minutes. Thepolymer was then filtered and dried at 60° C. in a forced air oven,yielding 11.4 g of the alkylated polymer. The polymer was ground andpassed through a 140 mesh sieve.

Example 22 Preparation of Poly(diallylammonium Chloride)

[0103] 100 g diallylamine and 100 mL deionized water were placed in a 1liter beaker and the mixture was allowed to stir. To this stirredmixture, 37% aqueous HCl was added slowly with concurrent measurement ofpH. When the pH of the solution dropped below 7, addition of acidstopped. The solution was extracted with 600 mL diethyl ether. To theaqueous solution, 3 g 2,2′-azobis(2-amidinopropane) dihydrochloride wasadded and the solution was bubbled with nitrogen gas for 45 minutes. Thesolution was then heated to 70° C. for 48 hr, after which time thereaction mixture has turned viscous. Heating was discontinued and, aftercooling to room temperature, 315 g of polymer solution was obtained.

Example 23 Synthesis of Insoluble Crosslinked Polydiallylamine

[0104] The polydiallylammonium chloride solution of Example 23 (150 g)was diluted with 50 mL deionized water. Solid NaOH (6.75 g) was added tothe polymer solution with stirring. The reaction mixture was stirreduntil the NaOH has dissolved and temperature of the solution had droppedto below 30° C. To this partially neutralized polymer solution,epichlorohydrin (1.2 mL) was added and stirring was continued. Thereaction medium slowly became increasingly viscous and after about 50minutes it gelled and the stirring stopped. This gelled polymer was leftat room temperature for an additional 48 hr to yield a semi-brittlepolymer slab. The polymer slab was broken into smaller pieces and wasdispersed in 1 L deionized water. The resulting suspension was stirredfor 1.5 hr and then filtered. The swollen polymer particles wereresuspended in 1 L deionized water and the suspension was stirred for 40minutes. The polymer particles were filtered off and dried in a forcedair oven at 60° C. to yield 56 g of pale white solid polymer. The driedpolymer was ground and passed through a 10 mesh sieve.

Example 24 Alkylation of Crosslinked Polydiallylamine with1-bromododecane

[0105] The ground polymer of Example 23 (5 g) was placed in a 500 mL3-necked round-bottomed flask and suspended in 100 mL deionized waterand the suspension was stirred with a mechanical stirrer. To thisswollen gel, a solution of 15 g 1-bromodecane in 100 mL ethanol wasadded and the reaction mixture was stirred for 10 minutes. 2 g 50%aqueous sodium hydroxide was then added and the reaction mixture wasstirred at room temperature for 40 minutes followed by heating to 75° C.Subsequently, an additional 4 g 50% NaOH was added in a 1 g batch at aninterval of 1.5 hr (the base addition maintained a pH between 10 to 12).The reaction mixture was allowed to stir at 75° C. for a total period of20 hr. After cooling to 30° C., 2 mL concentrated HCl was added and themixture was stirred for 30 minutes. The polymer was filtered off andwashed with 500 mL deionized water and 500 mL methanol. The filteredpolymer particles were slurried in methanol (400 mL), stirred for 40minutes and reisolated by filtration. This process was then repeated.The polymer was suspended in 500 mL 2M NaCl solution and the suspensionwas stirred for 40 minutes. The polymer was filtered off and this NaCltreatment was repeated two more times. The fitered polymer cake waswashed with 500 mL deionized water and suspended in 500 mL deionizedwater. After stirring the suspension for 30 minutes, the polymer wasfiltered off and resuspended in 500 mL deionized water. The resultingsuspension was stirred for 30 minutes. 1 mL concentrated HCl was addedto the suspension, which was then stirred for 35 minutes. The pH of thesuspension was found to be 2.2. The polymer was then filtered off anddried at 60° C. in a forced air oven, yielding 13.3 g of the alkylatedpolymer as a pale white solid. The polymer was ground and passed througha 140 mesh sieve.

Example 25 Alkylation of Crosslinked Polydiallylamine with(3-chloropropyl) Dimethyldodecylammonium Bromide

[0106] A mixture of 5 g of the crosslinked polymer gel of Example 23 and28 g (3-chloropropyl)dimethyl-dodecylammonium bromide was dispersed in150 nL deionized water and the suspension was stirred. To thissuspension 2 g 50% NaOH was added and the mixture was stirred for 15minutes. The mixture was then heated with stirring to 75° C. Anadditional 4 g 50% NaOH was added in 1 g batches at 1.5 hr intervals(the base addition was such as to maintain the pH between 10 to 12).After stirring at 75° C. for a total period of 18 hr, the reactionmixture was allowed to cool. After cooling to 30° C., 2 mL concentratedHCl was added and the mixture was stirred for 30 minutes. The polymerparticles were filtered off and washed with 200 mL methanol. Thefiltered polymer particles were suspended twice in methanol (400 mL) andthe suspension was stirred for 40 minutes. This process was repeated.After removing the polymer by filtration, the polymer was suspended in500 mL 2M NaCl solution and the suspension was stirred for 40 minutes.This NaCl treatment was repeated twice and the filtered polymer wassuspended in 500 mL deionized waer. The mixture was stirred for anadditional 45 minutes, filtered, resuspended in 400 mL deionized waterand stirred for another 40 minutes. To this suspension, 1 mLconcentrated HCl was added and the mixture was stirred for 20 minutes.The polymer was filtered off and dried in a forced air oven at 60° C.,yielding 13.2 g of alkylated polymer as a light yellow solid which wasground and passed through a 140 mesh sieve.

Example 26 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromooctane

[0107] The 3% crosslinked poly(diallylmethylamine) of Example 6 (5 g)was taken in a 500 mL 3-necked round-bottomed flask and suspended in 110mL deionized water. The polymer swelled significantly and was stirredwith a mechanical stirrer. To this swollen gel, a solution of 11.1 g1-bromooctane in 50 mL ethanol was added and the reaction mixture wasstirred for 10 minutes. 1 g 50% aqueous sodium hydroxide was then addedand the reaction mixture was stirred at room temperature for 40 minutesfollowed by heating to 75° C. for 1.5 hr. 1 g NaOH solution was added,and the reaction mixture was allowed to stir at 75° C. for an additional18 hr. After the mixture had cooled to 30° C., 2.5 mL concentrated HClwas added and the mixture was stirred for 30 minutes. The polymer wasfiltered and washed with 300 mL deionized water and 300 mL methanol.Polymer particles were suspended in 300 mL methanol and the suspensionwas stirred for 40 minutes. After removing the polymer by filtration,the polymer was suspended in 300 mL 2 M NaCl solution and the suspensionwas stirred for 40 minutes. The polymer was filtered off and this NaCltreatment was repeated two more times. The filtered polymer cake waswashed with 400 mL deionized water, then suspended in 400 mL deionizedwater. After the suspension was stirred for 30 minutes, it was filteredand the polymer was resuspended in 400 mL deionized water and thissuspension was stirred for an additional 30 minutes. 1 mL concentratedHCl was added to the suspension, which was then stirred for 30 minutes.The polymer was filtered and dried at 60° C. in a forced air oven,yielding 7.0 g of the alkylated polymer as a pale white solid. Thepolymer was ground and passed through a 140 mesh sieve.

Example 27 Alkylation of Crosslinked Poly(diallylmethylamine) with1-bromotetradecane

[0108] The 3% crosslinked poly(diallylmethylamine) of Example 6 (5 g)was taken in a 500 mL 3-necked round bottomed flask and suspended in 100mL deionized water. The polymer swelled significantly and was stirredwith a mechanical stirrer. To this swollen gel, 16 g 1-bromotetradecanedissolved in 40 mL ethanol was added and the reaction mixture wasstirred for 10 minutes. 1 g 50% aqueous sodium hydroxide was then addedand the reaction mixture was stirred at room temperature for 40 minutesfollowed by heating to 75° C. for 1.5 hr. 1 g NaOH solution was thenadded and the reaction mixture was stirred at 75° C. for additional 18hr. After cooling to 30° C., 2.5 mL concentrated HCl was added and themixture was stirred for 30 minutes. The polymer was filtered and washedwith 300 mL deionized water and 300 mL methanol. Polymer particles weresuspended in 300 mL methanol and the suspension was stirred for 40minutes. After removing the polymer by filtration, the polymer wassuspended in 300 mL 2M NaCl solution and the suspension was stirred for40 minutes. The polymer was filtered off and this NaCl treatment wasrepeated two more times. The filtered polymer cake was washed with 400mL deionized water and suspended in 400 mL deionized water. Afterstirring for 30 minutes the suspension was filtered and the polymer wasresuspended in 400 mL deionized water. This suspension was stirred foran additional 30 minutes. 1 mL concentrated HCl was then added to thesuspension and stirring continued for 30 minutes. The polymer wasfiltered off and dried at 60° C. in a forced air oven, yielding 9.0 g ofthe alkylated polymer as a pale white solid. The polymer was ground andpassed through a 140 mesh sieve.

Example 28 Alkylation of Crosslinked Poly(diallylmethylamine) with(3-chloropropyl)dimethyloctadecylammonium bromide

[0109] (3-Chloropropyl)dimethyloctadecylammonium bromide was prepared bythe general method of Example 10 starting with dimethyloctadecylamine. Amixture of the crosslinked polymer gel of Example 6 and 35 g(3-chloropropyl)dimethyloctadecylammonium bromide was dispersed in 150mL deionized water and the mixture was heated to 70° C. with stirringfor 15 minutes. 2 g 50% aqueous solution of NaOH and 50 mL ethanol werethen added to the reaction mixture. After 2 hr, 0.5 g NaOH solution wasadded and the reaction mixture was stirred at 70° C. for 20 hr. When thereaction mixture had cooled to 30° C., 2 mL concentrated HCl was addedand the mixture was stirred for another 20 minutes. The polymer wasfiltered off and washed with 200 mL deionized water and 200 mL methanol.The filtered polymer particles were dispersed in 500 mL methanol,stirred for another 30 minutes and then filtered. This process wasrepeated one more time and the filtered polymer was suspended in 300 mL2M NaCl solution. The resulting suspension was stirred for another 45minutes and filtered. After repeating the NaCl treatment twice, thefiltered polymer was suspended in 400 mL deionized water. The mixturewas stirred for 30 minutes, filtered, and the polymer was resuspended in400 mL deionized water. The suspension was stirred for an additional 40minutes. To this suspension was added 1 mL concentrated HCl and themixture was stirred for 20 minutes. The polymer was filtered and driedin a forced air oven at 60° C., yielding 10.7 g alkylated polymer as apale white solid which was ground and passed through a 140 mesh sieve.

Example 29 Alkylation of Crosslinked Poly(diallylmethylamine) with(3-Chloropropyl)dodecylpyrrolidiniumammonium bromide

[0110] Synthesis of (3-chloropropyl)dodecylpyrrolidinium Bromide

[0111] 47 g pyrrolidine, 149.5 g 1-bromododecane and 83 g potassiumcarbonate were added to 560 mL acetone. The reaction mixture was heatedat 55° C. for 24 hr, then filtered. Solvent was removed from thefiltrate, yielding 92 g N-dodecylpyrrolidine. 80 g N-dodecylpyrrolidineand 52.6 g 1-bromo-3-chloropropane were dissolved in 133 mL methanol andthe reaction mixture was heated at 65° C. for 18 hr. After cooling toroom temperature, methanol was removed under reduced pressure. Theresidue was poured into 2 L diethylether with stirring and the mixturewas allowed to stand for another 6 hr. The white precipitate thus formedwas filtered and was dried at 40° C. under a vacuum for 24 hr yielding85 g (3-chloropropyl)dodecylpyrrolidinium bromide as a white solid.

[0112] Alkylation of Crosslinked Poly(diallylmethylamine) with(3-chloropropyl) Dodecylpyrrolidinium Bromide

[0113] The 3% crosslinked poly(diallylmethylamine) of Example 7 (5 g)and 30 g (3-chloropropyl)dodecyl-pyrrolidinium bromide were dispersed in150 mL deionized water and the mixture was heated to 70° C. withstirring. After stirring at 70° C. for 15 minutes, 2 g 50% aqueous NaOHsolution was added to the reaction mixture. After 2 hr, 1 g NaOHsolution was added and the reaction mixture was allowed to stir at 70°C. for 20 hr. The reaction mixture was then allowed to cool to 30° C. 2mL concentrated HCl was then added and the mixture was stirred for 20minutes. The polymer was filtered off and washed with 200 mL deionizedwater and 200 mL methanol. The polymer particles were dispersed in 500mL methanol and the suspension was stirred for 30 minutes and thenfiltered. This process was repeated one more time and the filteredpolymer was suspended in 300 mL 2M NaCl solution. The resultingsuspension was stirred for 45 minutes and filtered. After repeating thisNaCl treatment twice, the filtered polymer was suspended in 400 mLdeionized water. The mixture was stirred for 30 minutes, filtered,resuspended in 400 mL deionized water and stirred for an additional 40minutes. To this polymer suspension was added 1 mL concentrated HCl andstirring continued for an additional 20 minutes. The polymer wasfiltered off and dried in a forced air oven at 60° C., yielding 13 galkylated polymer as a pale white solid which was ground and passedthrough a 140 mesh sieve.

Example 30 Alkylation of Crosslinked Poly(diallylmethylamine) with(3-Chloropropyl)dodecylpiperidinium bromide

[0114] Synthesis of (3-chloropropyl)decylpiperidinium Bromide

[0115] N-decylpiperidine was synthesized by reacting 45.7 g piperidinewith 118.7 g 1-bromodecane in 237 mL acetone in the presence of 74 gpotassium carbonate. After refluxing this reaction mixture at 55° C. for24 hr, it was filtered and acetone was removed from the filtrate toyield 61 g N-decylpiperidine. 5 g N-decylpiperidine and 42 g1-bromo-3-chloropropane were dissolved in 50 mL methanol and thereaction mixture was heated at 65° C. for 18 hr. After cooling to roomtemperature, methanol was removed under reduced pressure. The residuewas poured into 2 L tert.butylmethyl ether with stirring and then themixture was allowed to stand for 6 hr. The white precipitate thus formedwas filtered and was dried at 40° C. under vacuum for 24 hr yielding 68g (3-chloropropyl)decylpiperidinium bromide as a light yellow solid.

[0116] Alkylation of Crosslinked Poly(diallylmethylamine) with(3-chloropropyl) Decylpiperidinium Bromide

[0117] The 3% crosslinked poly(diallylmethylamine) of Example 6 (5 g)and 32 g (3-chloropropyl) decylpiperidiniumammonium bromide weredispersed in 150 mL deionized water and the reaction mixture was heatedto 70° C. with stirring for 15 minutes. 2 g 50% aqueous solution of NaOHwas then added to the reaction mixture. After 2 hr, 1 g NaOH solutionwas added and the reaction mixture was allowed to stir at 70° C. for 20hr. When the reaction mixture had cooled to 30° C., 2 mL concentratedHCl was added and the mixture was stirred for 20 minutes. The polymerwas filtered off and washed with 200 mL deionized water and 200 mLmethanol. The polymer particles were dispersed in 500 mL methanol andthe suspension was stirred for an additional 30 minutes, then filtered.This process was repeated once and the polymer was suspended in 300 mL2M NaCl solution. The suspension was stirred for 45 minutes andfiltered. After repeating this NaCl treatment twice, the filteredpolymer was suspended in 400 mL deionized water. The mixture was stirredfor 30 minutes, filtered, resuspended in 400 mL deionized water and thesuspension was stirred for 40 minutes. To this polymer suspension wasadded 1 mL concentrated HCl and the mixture was stirred for 20 minutes.The polymer was filtered off and dried in a forced air oven at 60° C.,yielding 13.2 g alkylated polymer as a pale white solid which was groundand passed through a 140 mesh sieve.

Example 31 Alkylation of Crosslinked Poly(diallylmethylamine) with(4-Chlorobutyl)diethyldecylammonium bromide

[0118] (4-Chlorobutyl)diethyldecylammonium bromide was prepared by thegeneral method of Example 10 using 4-chloro-1-bromobutane anddecyldiethylamine. The 3% crosslinked poly(diallylmethylamine) ofExample 6 (5 g) and 22 g (4-chlorobutyl) diethyldecylammonium bromidewere dispersed in 150 mL deionized water and the resulting mixture washeated to 70° C. with stirring for 15 minutes. 2 g 50% aqueous solutionof NaOH was then added to the reaction mixture. After 2 hr, 0.5 g NaOHsolution was added and the reaction mixture was allowed to stir at 70°C. for 20 hr. When the reaction mixture had cooled to 30° C., 2 mLconcentrated HCl was added and the mixture was stirred for an additional20 minutes. The polymer was filtered off and washed with 200 mLdeionized water and 200 mL methanol. The polymer particles weredispersed in 500 mL methanol and the suspension was stirred for 30minutes and then filtered. This process was repeated once and thefiltered polymer was suspended in 300 mL 2M NaCl solution. Thesuspension was stirred for an additional 45 minutes and filtered. Afterrepeating this NaCl treatment twice, the filtered polymer was suspendedin 400 mL deionized water and the mixture was stirred for an additional40 minutes. To this polymer suspension was added 1 mL concentrated HCland the mixture was stirred for 20 minutes. The polymer was filtered offand dried in a forced air oven at 60° C., yielding 10.6 g alkylatedpolymer as a pale white solid which was ground and passed through a 140mesh sieve.

Example 32 Alkylation of Crosslinked Poly(diallylmethylamine) withVarying Amounts of (3-Chloropropyl)dimethyl-dodecylammonium Bromide

[0119] This example illustrates alkylation of the 3% crosslinkedpoly(diallylmethylamine) of Example 6 with different amounts of(3-chloropropyl)dimethyldodecylammonium bromide. For this purpose, thepolymer was treated with varying mole fractions of the alkylating agent(1.0, 0.75, 0.50, 0.25 and 0.10) via the general procedure described inExample 9. Table 2 summarizes amounts of (3-chloropropyl)dimethyldodecylammonium bromide used to obtain polymers of varyingdegree of alkylation and yield of alkylated polymer per gram of the 3%crosslinked poly(diallylmethylamine). This g/g yield is a measure of thedegree of alkylation of the polymer. TABLE 2 Results of the alkylationof 3% crosslinked poly(diallylmethylamine) with varying amounts of(3-chloropropyl)dimethyldodecylammonium bromide (C₁₂QC₃C₁Br). PolymerAlkylating Mole frctn of Yield of used (g) agent used (g) alkylatingagent alkylated Yield (g/g) 5.0 14.25 1.0 11.3 2.3 5.0 10.7 0.75 8.3 1.75.0 7.1 0.50 7.0 1.40 5.0 3.6 0.25 6 1.20 5.0 1.40 0.10 5.1 1.02

Example 33 Synthesis of 1,4-butanediol Diglycidyl Ether CrosslinkedPoly(diallylmethylamine)

[0120] 33.2 g the 60% solution of poly(diallylmethylamine) (PAS-M-1, Lot#51017) was diluted with 68 mL D.I. water. While stirring, 2.8 g NaOHwas added to the polymer solution. The reaction mixture was allowed tostir until all NaOH had dissolved. When the temperature of the solutionhas dropped to below 30° C., 1.25 g 1,4-butanediol diglycidyl ether wasadded and stirring continued. The reaction medium slowly becameincreasingly viscous and after about 45 minutes it gelled and thestirring was stopped. The polymer gel was left at room temperature foran additional 48 hours. The polymer slab was broken into smaller piecesand was dispersed in 300 mL D.I. water. The suspension was stirred for30 minutes and was filtered. The swollen polymer particles wereresuspended in 400 mL D.I. water, stirred for 1 hr and filtered. Thisprocess was repeated twice more. The filtered polymer (swollen gel) wasdried in a forced air oven at 60° C. to yield 15 g of the product.

Example 34 Alkylation of 1,4-butanediol diglycidyl Ether CrosslinkedPoly(diallyl- methylamine) with 1-bromodecane

[0121] 5 g of the ground polymer (Example 33) was placed in a 500 mL3-necked round-bottomed flask was suspended in 100 mL D.I. water. Thepolymer swelled significantly and was stirred with a mechanical stirrer.To this swollen gel, 12 g 1-bromodecane dissolved in 100 mL ethanol wasadded and the reaction mixture stirred for 10 minutes. Subsequently, 1 g50% aqueous sodium hydroxide was added and the reaction mixture wasstirred at room temperature for 40 minutes followed by an additional 0.5g of NaOH solution after another 1.5 hr (the base addition was such asto maintain the pH between 10 and 12). The reaction mixture was allowedto stir at 75° C. for an additional 18 hrs after which time heating wasdiscontinued. After cooling to 30° C., 2 mL concentrated HCl was addedand stirring for 30 minutes continued. The pH of the suspension droppedto 1.8. The polymer was filtered and washed with 250 mL D.I. waterfollowed by 250 mL methanol. Polymer particles were suspended in 300 mLmethanol and stirred for 40 minutes. After removing the solvent byfiltration, the polymer was suspended in 250 mL 2M NaCl solution andstirred for an additional 40 minutes. It was filtered and this processof NaCl treatment was repeated two more times. The filtered polymer cakewas washed with 250 mL D.I. water and suspended in 250 mL D.I. water.After stirring for 30 minutes it was filtered and resuspended in 400 mLD.I. water and stirred for an additional 30 minutes. 2 mL conc. HCl wasadded to the suspension and stirred for another 15 minutes. The pH ofthe suspension was found to be 2.10. After stirring for an additional 20minutes, the polymer was filtered and dried at 60° C. in a forced airoven yielding 9 g of the alkylated polymer as a pale white solid. Thepolymer was ground and passed through a 140 mesh sieve.

Example 35 Reaction of Poly(diallylmethylamine) with (4-chlorobutyl)Dimethyldodecyl Ammonium Bromide

[0122] A solution of poly(diallylmethylamine) hydro-chloride (8.38 g ofa 60% polymer solution in water), NaOH (5.5 g of a 50% NaOH solution inwater), deionized water (150 mL) and (4-chlorobutyl)dimethyldodecylammonium bromide (26.2 g) was heated to 75° C. for 24 hours. Aftercooling to room temperature, the mixture was filtered. The solid waswashed on the funnel with deionized water (1.5 L). The solid wassuspended again in 2 M NaCl (1.0 L), stirred for 30 minutes, and thenfiltered. The solid was suspended again in 2 M NaCl (1.0 L), stirred for30 minutes, and then filtered. The solid was suspended again in 2 M NaCl(1.0 L), stirred for 30 minutes, and then filtered. The solid was washedon the funnel with deionized water (2.0 L). The solid was suspended indeionized water (1.0 L), and concentrated HCl (1.4 mL) was added to thissuspension. After stirring 1 hour, this suspension was filtered. Thematerial was dried in a forced air oven at 60° C. for 24 hours to afford19.1 g of product.

Example 36 Reaction of Poly(diallylmethylamine) with 1-bromodecane

[0123] To a solution of poly(diallylmethylamine) hydro-chloride (16.7 gof a 60% polymer solution in water), NaOH (5.5 g of a 50% NaOH solutionin water), deionized water (100 mL), and ethyl alcohol (100 mL) wasadded 1-bromodecane (44.4 g). This solution was then heated to 75° C.for 24 hours. After the first 2 hours of heating, NaOH (1.0 g of a 50%NaOH solution in water) was added. After cooling to room temperature,the mixture was evaporated on a rotary evaporator to remove the ethylalcohol. Water (500 mL) was added to the mixture, and the mixture wasfiltered. The solid was washed on the funnel with deionized water (1.0L). The solid was suspended in 2M NaCl (1.0 L), stirred for 30 minutes,and then filtered. The solid was suspended again in 2 M NaCl (1.0 L),stirred for 30 minutes, and then filtered. The solid was suspended againin 2 M NaCl (1.0 L), stirred for 30 minutes, and then filtered. Thesolid was washed on the funnel with deionized water (2.0 L). The solidwas suspended in deionized water (1.0 L) and concentrated HCl (2.4 mL)was added to this suspension, and after stirring 1 hour, this suspensionwas filtered. The material was dried in a forced air oven at 60° C. for24 hours to afford 20.8 g of product.

Example 37

[0124] A suspension of the product from Example 36 (5.01 g), methylalcohol (100 mL), iodomethane (7.4 mL), and NaOH (1.0 g of a 50% NaOHsolution in water) was stirred at room temperature for 24 hours. Afterthe first 7 hours of reaction, iodomethane (7.4 mL) was added. After the24 hour reaction period at room temperature, NaOH (1.0 g of a 50% NaOHsolution in water) was added, and the mixture was heated to 50° C. for 4hours. After one hour of heating, NaOH was added (1.0 g of a 50% NaOHsolution in water). After the first 2.5 hours of heating (0.5 g of a 50%NaOH solution in water), NaOH was again added. After cooling to roomtemperature, methyl alcohol (100 mL) was added to the mixture, and themixture was evaporated on a rotary evaporator to remove the methylalcohol. The solid was suspended in 2M NaCl (1.0 L), stirred for 30minutes, and then filtered. The solid was suspended again in 2M NaCl(1.0 L), stirred for 30 minutes, and then filtered. The solid wassuspended again in 2M NaCl (1.0 L), stirred for 30 minutes, and thenfiltered. The solid was washed on the funnel with deionized water (4.0L). The solid was suspended in deionized water (1.0 L) and concentratedHCl (50 drops) was added to this suspension, and after stirring 30minutes, this suspension was filtered. The material was dried in aforced air oven at 60° C. to afford 5.2 g of product.

Example 38

[0125] A suspension of the product from Example 35 (5.01 g), methylalcohol (100 mL), iodomethane (7.0 mL), and NaOH (1.0 g of a 50% NaOHsolution in water) was stirred at room temperature for 24 hours. After 7hours of reaction, iodomethane (7.0 mL) was added. Following a 24 hourreaction period at room temperature, NaOH (1.0 g of a 50% NaOH solutionin water) was added, and the mixture was heated to 50° C. for 4 hours.After the first hour of heating, NaOH was added (1.0 g of a 50% NaOHsolution in water). After 2.5 hours of heating, NaOH was again added(0.5 g of a 50% NaOH solution in water). After cooling to roomtemperature, methyl alcohol (100 mL) was added to the mixture, and themixture was evaporated on a rotary evaporator to remove the methylalcohol. The solid was suspended in 2M NaCl (1.0 L), stirred for 30minutes, and then filtered. The solid was suspended again in 2M NaCl(1.0 L), stirred for 30 minutes, and then filtered. The solid wassuspended again in 2M NaCl (1.0 L), stirred for 30 minutes, and thenfiltered. The solid was washed on the funnel with deionized water (4.0L). The solid was suspended in deionized water (1.0 L), and concentratedHCl (50 drops) was added to this suspension. After stirring 30 minutes,this suspension was filtered. The material was dried in a forced airoven at 60° C. to afford 4.9 g of product.

Example 39 In Vivo Testing

[0126] The polymers produced in Examples 35-37 were tested in vivo,using the following protocol. After a week of acclimation to thefacility, the animals were transferred to special cages that separateurine and feces. They were given only water for a 24 hour period inorder to synchronize their urge for food as a drug. The food waspresented for a 72 hour period. Fecal material was collected for 63hours, from the hour 9 to hour 72 post presentation. The fecal materialwas freeze-dried to eliminate water from the material. It was pulverizedwith an amalgamator to a uniform powder, and 1 g was placed in theextraction cell. A solution of 80% methanol 100 mMol NaOH was used asthe extraction solvent. The extraction was accelerated by holding thesample and solvent at 100° C. and 1500 psi for 5 minutes. The extractionwas evaporated and reconstituted in bovine calf serum. The concentrationwas multiplied by four times the volume of extract and expressed as theconcentration per gram of feces.

[0127] It is clear from the results shown in Table 3 that thesesequestrants are highly active in vivo, with efficacy far surpassing thecommercial bile acid sequestrant cholestyramine. TABLE 3 In VivoEfficacy of Polymers of Examples 35-37 Bile Acid Excretion (μmole/gPolymer Dose (Percent in Diet) feces above control) None   0% 0Cholestyramine  0.3% 1.7 0.60% 4.8 0.90% 6.3 1.20% 7.5 Example 35 0.10%1.40 Example 36 0.10% 3.7 Example 37 0.10% 2.5

Example 40

[0128] In a 5 mL three necked round bottom flask was taken 10 g of thecrosslinked poly(diallylmethylamine) of Example 6. To this was added 200mL of deionized water. While stirring, 2 g of 50% aqueous NaOH solutionwas added to this polymer suspension. After stirring for 15 minutes,13.6 g of 1-chlorodecane was added and the reaction mixture was heatedto 90° C. with stirring. After 1.5 hr of heating, 1.0 g of reagant ofthe NaOH solution was added to the reaction mixture followed by anadditional 0.5 g of the NaOH after another 2 hr. After stirring at 90°C. for a total period of 18 hr, the reaction mixture was allowed to coolto room temperature. Concentrated HCl (5 mL) was added to the reactionmixture and stirred for 30 minutes. The polymer was filtered and waswashed with 500 mL of methanol. The polymer particles were suspended in1 L of methanol, stirred for 30 minutes and filtered. After repeatingthis methanol washing once more, the polymer particles were suspended in1 L of deionized water. The suspension was stirred for 30 minutes andfiltered. The polymer particles were resuspended in 1 L of deionizedwater and stirred for 15 minutes. To this suspension was added 3 mL ofconcentrated HCl and the stirring continued for an additional 30minutes. The particles were filtered and dried in a forced air oven at60° C., yielding 16 g of the alkylated polymer as light yellowish solid.The polymer was ground and passed through a 140 mesh sieve.

Example 41

[0129] This Example illustrates the role of the reaction temperatureduring alkylation of crosslinked of poly(diallylmethylamine) with1-chlorodecane. For this purpose, the alkylation reactions were carriedout at 70° C., 80° C., 90° and 100° C. The amount of 1-chlorodecane usedand the reaction time was kept unchanged for all the reactions. Yield ofthe alkylated polymer thus obtained at these reactions temperatures aresummarized in Table 4.

[0130] In a 500 mL three necked round bottomed flask was taken 10 g ofthe crosslinked poly(diallylmethylamine) (Example 6). To this was added200 mL of deionized water. While stirring, 2 g of 50% aqueous NaOHsolution was added to this polymer suspension. After stirring for 15minutes, 13.6 g of 1-chlorodecane was added and the reaction mixtureheated to the appropriate temperature with stirring. After 1.5 hr ofheating, 1.0 g of reagent of the NaOH solution was added to the reactionmixture followed by an additional 0.5 g of the NaOH after another 2 hr.After stirring at the appropriate temperature for a total period of 18hr, the reaction mixture was allowed to cool to room temperature.Concentrated HCl (5 mL) was added to the reaction mixture and stirredfor 30 minutes. The polymer was filtered and was washed with 500 mL ofmethanol. The polymer particles were suspended in 1 L of methanol,stirred for 30 minutes and filtered. After repeating this methanolwashing once more, the polymer particles were suspended in 1 L ofdeionized water. The suspension was stirred for 30 minutes and filtered.The polymer particles were resuspended in 1 L of deionized water andstirred for 15 minutes. To this suspension was added 3 mL ofconcentrated HCl and the stirring continued for an additional 30minutes. The particles were filtered and dried in a forced air oven at60° C. Yield of the alkylated polymers obtained at different reactiontemperatures are summarized in Table 4. All the polymers were ground andpassed through a 140 mesh sieve. TABLE 4 Results on the role of thereaction temperature on the alkylation of 4.5% epichlorohydrincrosslinked poly(diallylmethylamine with 1-chlorodecane. Reaction1-Chlorodecane used Temperature Product Polymer used (g) (g) (° C.)Yield (g) 10 13.6 70 11.6 10 13.6 80 13.5 10 13.6 90 16.0 10 13.6 10017.0

Example 42

[0131] This Example illustrates the role of the amounts of the1-chlorodecane used in the alkylation of 4.5% epichlorohydrincrosslinked poly(diallylmethylamine) to prepare polymers with differentdegrees of alkylation. For this purpose, the polymer was treated withvarying mole fractions of 1-chlorodecane (1.0, 0.5 and 0.25). Allalkylation reactions were carried out at 90° C. for a period of 18 hr.Table 5 summarizes the amounts of 1-chlorodecane used to obtain polymersof varying degrees of alkylation and the yield of the correspondingalkylated polymers.

[0132] In a 500 mL three necked round bottomed flask was taken 10 g ofthe crosslinked poly(diallylmethylamine) (example 6). To this was added200 mL of deionized water. While stirring, 2 g of 50% aqueous NaOHsolution was added to this polymer suspension. After stirring for 15minutes, appropriate amount of 1-chlorodecane was added and the reactionmixture heated to 90° C. with stirring. After 1.5 hr of heating, 1.0 gof reagent of the NaOH solution was added to the reaction mixturefollowed by an additional 0.5 g of the NaOH after another 2 hr. Afterstirring at 90° C. for a total period of 18 hr, the reaction mixture wasallowed to cool to room temperature. Concentrated HCl (5 mL) was addedto the reaction mixture and stirred for 30 minutes. The polymer wasfiltered and was washed with 500 mL of methanol. The polymer particleswere suspended in 1 L of methanol, stirred for 30 minutes and filtered.After repeating this methanol washing once more, the polymer particleswere suspended in 1 L of deionized water. The suspension was stirred for30 minutes and filtered. The polymer particles were resuspended in 1 Lof deionized water and stirred for 15 minutes. To this suspension wasstirred for 30 minutes. The particles were filtered and dried in aforced air oven at 60° C. Yield of the alkylated polymers obtained fordifferent alkylation levels are summarized in Table 5. All the polymerswere ground and passed through a 140 mesh sieve. TABLE 5 Results of thealkylation of 4.5% epichlorohydrin crosslinked polydiallymethyl-aminewith varying amounts of 1-chlorodecane. Polymer 1-Chlorodecane usedReaction Product Yield used (g) (g) Temperature (° C.) (g) 10 3.4 9012.2 10 6.8 90 14.5 10 10.2 90 15.7 10 13.6 90 16.0

Example 43

[0133] Non-crosslinked Polydiallylamine hydrochloride (PDA-HCl) andnon-crosslinked Poly(diallylmethylamine) hydrochloride (PDMA-HCl) werereacted with a variety of crosslinking agents and alkylating agents.Table 6 gives details of the crosslinking and alkylating agents,reaction conditions and yields (IPA=isopropyl alcohol;PDA=poly(diallylamine), PDMA=poly(diallylmethylamine)). The reactionsconditions are analogous to those described in Example 42 wherecrosslinked poly(diallylmethylamine) was reacted with 1-chlorodecane.TABLE 6 Solvent Time Example Reactants (amount) (amount) Temperature(hr) Yield 43 PDMA.HCl (100.0 g of 60% ag H₂O 75° C. 18 88 soln),1-bromodecane (62.9 g), (600) mL epichlorohydrin (4.77 mL), NaOH (32.5 gof 50% aq soln) 44 PDMA.HCl (100.0 g of 60% aq IPA 75° C. 18 99 soln),1-bromodecane (62.9 g), (100 mL) 1,6-dibromohexane (9.37 mL), H₂O NaOH(5 addns of 6.5 g of 50% aq (500 mL) soln) 45 PDMA.HCl (100.0 g of 60%aq IPA 75° C. 18 92 soln), 1-bromodecane (62.9 g), (100 mL)epichlorohydrin (4.77 mL), NaOH H₂O (32.5 g of 50% ag soln) (500 mL) 46PDA.HCl (103.7 g of 52.3% aq IPA 75° C. 18 53 soln), 1-bromodecane (62.9g), (100 mL) epichlorohydrin (4.77 mL), NaOH (7 H₂O addns for a total of45 g of 50% aq (100 mL) soln) 47 PDA.HCl (103.7 g of 52.3% aq IPA 75° C.18 67 soln), 1-bromodecane (62.9 g), (100 mL) epichlorohydrin (4.77 mL),NaOH (90 g of 50% aq soln) 48 PDA.HCl (103.7 g of 52.3% aq IPA 75° C. 1862 soln), 1-bromodecane (62.9 g), (100 mL) epichlorohydrin (4.77 mL),NaOH (4 addns of 13.8 g of 50% aq soln) 49 PDA.HCl (103.7 g of 52.3% aqIPA 75° C. 18 64 soln), 1-bromodecane (62.9 g), (100 mL) epichlorohydrin(4.77 mL), NaOH H₂O (135.0 g of 50% ag soln) (100 mL) 50 PDA.HCl (92.0 gof 59% aq soln), IPA 75° C. 18 90 1-bromodecane (62.9 g), 1,6- (100 mL)dibromohexane (9.37 mL), NaOH H₂O (90.0 g of 50% aq soln) (100 mL) 51PDA.HCl (95.3 g of 57% aq soln), IPA 75° C. 18 52 1-bromodecane (62.9g), (100 mL) epichlorohydrin (4.77 mL), HaOH H₂O (90 g of 50% aq soln)(100 mL) 52 PDA.HCl (92.0 g of 57% aq soln), IPA 75° C. 18 871-bromodecane (62.9 g), (100 mL) epichlorohydrin (4.77 mL), NaOH H₂O (90g of 50% aq soln) (100 mL) 53 PDA.HCl (92.0 g of 57% aq soln), IPA 75°C. 18 60 1-bromodecane (62.9 g), (100 mL) epichlorohydrin (6.35 mL),NaOH H₂O (90.0 g of 50% aq soln) (100 mL) 54 PDA.HCl (95.6 g of 56.8% aqsoln), IPA 75° C. 18 71 1-bromodecane (62.9 g), (100 mL)1,6-dibromohexane (3.12 mL), H₂O NaOH (90.0 g of 50% aq soln) (100 mL)55 PDA.HCl (95.6 g of 56.8% aq soln), IPA 75° C. 18 73 1-bromodecane(62.9 g), (100 mL) epichlorohydrin (1.59 mL), NaOH H₂O (90 g of 50% aqsoln) (100 mL) 56 PDA.HCl (54.3 g of 59% aq soln), H₂O 95° C. 18 581-chlorodecane (50.2 g), (200 mL) epichlorohydrin (1.59 mL), NaOH (90 gof 50% aq soln) 57 PDA.HCl (100.0 g of 60% aq soln), H₂O 75° C. 18 861-bromodecane (62.9 g), (300 mL) epichlorohydrin (4.77 mL) NaOH IPA(32.5 g of 50% aq soln) (300 mL) 58 PDMA.HCl (100.0 g of 60% aq IPA 75°C. 18 85 soln), 1-bromodecane (62.9 g), (600 mL) epichlorohydrin (4.77mL), NaOH (32.5 g of 50% aq soln) 59 PDMA.HCl (100.0 g of 60% aq H₂O 75°C. 18 86 soln), 1-bromodecane (62.9 g), (600 mL) epichlorohydrin (0.318mL), NaOH (32.5 g of 50% aq soln) 60 PDMA.HCl (100.0 g of 60% aq H₂O 75°C. 18 74 soln), 1-bromodecane (31.5 g), (600 mL) epichlorohydrin (4.77mL), NaOH (32.5 g of 50% aq soln) 61 PDMA.HCl (100.0 g of 60% aq H₂O 75°C. 18 11 soln), 1,4-butanediol diglycidyl ether (300 mL) (11.74 mL),dodecyl/tetradecyl IPA glycidyl ether (86.4 mL), NaOH (300 mL) (32.5 gof 50% aq soln) 62 PDMA.HCl (100.0 g of 60% aq H₂O 75° C. 18 82 soln),1-bromododecane (62.9 g), (300 mL) epichlorohydrin (9.54 mL), NaOH IPA(32.5 g of 50% aq soln) (300 mL) 63 PDMA.HCl (100.0 g of 60% aq H₂O 75°C. 18 94 soln), 1-bromododecane (125.8 g), (300 mL) epichlorohydrin(4.77 mL), NaOH IPA (32.5 g of 50% aq soln) (300 mL) 64 PDMA.HCl (100.0g of 60% aq H₂O 75° C. 18 81 soln), 1-bromodecane (62.9 g), (300 mL)epichlorohydrin (9.54 mL), NaOH IPA (32.5 g of 50% aq soln) (300 mL) 65PDMA.HCl (100.0 g of 60% aq H₂O 75° C. 18 91 soln), 1-bromodecane (118.0mL), (300 mL) epichlorohydrin (4.77 mL), NaOH IPA (32.5 g of 50% aqsoln) (300 mL) 66 PDMA.HCl (100.0 g of 50% aq H₂O 75° C. 18 66 soln),1-bromododecane (35.8 g), (300 mL) epichlorohydrin (9.54 mL), NaOH IPA(32.5 g of 50% aq soln) (300 mL) 67 PDMA.HCl (100.0 g of 60% aq H₂O 75°C. 18 90 soln), 1-bromododecane (80.7 g), (300 mL) epichlorohydrin (1.59mL), NaOH IPA (32.5 g of 50% aq soln) (300 mL) 68 PDMA.HCl (100.0 g of60% aq H₂O 60° C. 18 39 soln), 1-bromodecane (62.9 g), (600 mL)epichlorohydrin (4.77 mL), NaOH hexanes (32.5 g of 50% aq soln) (1200mL) 69 PDMA.HCl (100.0 g of 60% aq toluene 75° C. 18 60 soln),1-bromodecane (62.9 g), (600 mL) epichlorohydrin (4.77 mL), NaOH (32.5 gof 50% aq soln) 70 PDMA.HCl (100.0 g of 60% aq MeOH 60° C. 18 49 soln),1-bromodecane (62.9 g), (600 mL) epichlorohydrin (4.77 mL), NaOH hexanes(32.5 g of 50% aq soln) (1200 mL) 71 PDMA.HCl (100.0 g of 60% aq H₂O 95°C. 18 82 soln), 1-chlorodecane (50.3 g), (600 mL) epichlorohydrin (4.77mL), NaOH (32.5 g of 50% aq soln) 72 PDMA.HCl (100.0 g of 60% aq H₂O 95°C. 18 75 soln), 1-chlorodecane (65.3 g), (600 mL) epichlorohydrin (1.43mL), NaOH (32.5 g of 50% aq soln) 73 PDMA.HCl (100.0 g of 60% aq H₂O 95°C. 18 66 soln), 1-chlorodecane (32.7 g), (600 mL) epichlorohydrin (1.43mL), NaOH (32.5 g of 50% aq soln) 74 PDMA.HCl (100.0 g of 60% aq H₂O 95°C. 18 59 soln), 1-chlorodecane (16.4 g), (600 mL) epichlorohydrin (1.43mL), NaOH (32.5 g of 50% aq soln)

[0134] While this invention has been particularly shown and describedwith references to preferred embodiments thereof, it will be understoodby those skilled in the art that various changes in form and details maybe made therein without departing from the spirit and scope of theinvention as defined by the appended claims.

What is claimed is:
 1. A method for removing bile acids from a patientcomprising the step of administering to the patient a therapeuticallyeffective amount of a poly(diallylamine) polymer wherein more than 10%of the amino nitrogen atoms are substituted by a hydrophobicsubstituent.
 2. The method of claim 1 wherein the polymer is ahomopolymer.
 3. The method of claim 1 wherein the polymer is acopolymer.
 4. The method of claim 1 wherein the hydrophobic substituentis a normal or branched C₂-C₂₄-alkyl group.
 5. The method of claim 1wherein the polymer comprises a repeat unit of the general formula

wherein R² is hydrogen, a substituted or unsubstituted C₁-C₂₄-alkylgroup, a substituted or unsubstituted arylalkyl group or a substitutedor unsubstituted aryl group; R¹ is a substituted or unsubstitutedC₃-C₂₄-alkyl group, a substituted or unsubstituted arylalkyl group or asubstituted or unsubstiuted aryl group; and X⁻ is a pharmaceuticallyacceptable anion.
 6. The method of claim 5 wherein X⁻ is a conjugatebase of an acid selected from the group consisting of hydrochloric acid,hydrobromic acid, citric acid, tartaric acid, lactic acid, phosphoricacid, methanesulfonic acid, acetic acid, formic acid, maleic acid,fumaric acid, malic acid, succinic acid, malonic acid, sulfuric acid,L-glutamic acid, L-aspartic acid, pyruvic acid, mucic acid, benzoicacid, glucuronic acid, oxalic acid, ascorbic acid and acetylglycine. 7.The method of claim 5 wherein R¹ is a normal or branched C₃-C₂₄-alkylgroup which is substituted by an amino group, an ammonium group, anamido group, a hydroxyl group, a sulfone group, a sulfoxide group or analkoxy group.
 8. The method of claim 5 wherein R¹ is an alkyl groupselected from the group consisting of hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, tridecyl and tetradecyl.
 9. The method of claim8 wherein R² is methyl and R¹ is selected from the group consisting ofoctyl, decyl and dodecyl.
 10. The method of claim 1 wherein the polymeris characterized by a repeat unit of the general formula

wherein R is a substituted or unsubstituted alkyl group or a substitutedor unsubstituted aryl group.
 11. The method of claim 10 wherein R is aC₃-C₂₄-alkyl group.
 12. The method of claim 11 wherein the alkyl groupis selected from the group consisting of hexyl, heptyl, octyl, nonyl,decyl, undecyl, dodecyl, tridecyl and tetradecyl.
 13. The method ofclaim 11 wherein the alkyl group is substituted by an amino group, anammonium group, an amido group, a hydroxyl group, a sulfoxide group, asulfone group or an alkoxy group.
 14. The method of claim 1 wherein thepolymer comprises a first monomer of the general formula

wherein R¹ is hydrogen, a substituted or unsubstituted C₁-C₂₄-alkylgroup or a substituted or unsubstituted aryl group; R² is a substitutedor unsubstituted C₃-C₂₄-alkyl group or a substituted or unsubstiutedaryl group; and X⁻ is a pharmaceutically acceptable anion; and a secondmonomer of the general formula

wherein R is hydrogen, a substituted or unsubstituted alkyl group or asubstituted or unsubstituted aryl group.
 15. The method of claim 1wherein the polymer is a crosslinked polymer.
 16. The method of claim 15wherein the polymer is crosslinked by a multifunctional co-monomer. 17.The method of claim 16 wherein the multifunctional co-monomer isselected from the group consisting of diacrylates, triacrylates,tetraacrylates, dimethacrylates, diacrylamides, dimethacrylamides,diallylacrylamides and polyvinylarenes.
 18. The method of claim 17wherein the multifunctional comonomer is selected from the groupconsisting of ethylene glycol diacrylate, propylene glycol diacrylate,butylene glycol diacrylate, ethylene glycol dimethacrylate, butyleneglycol dimethacrylate, methylene bis(methacrylamide), ethylenebis(acrylamide), ethylene bis(methacrylamide), ethylidenebis(acrylamide), ethylidene bis(methacrylamide), bisphenol Adimethacrylate, bisphenol A diacrylate, pentaerythritol tetraacrylate,trimethylolpropane triacrylate and divinylbenzene.
 19. The method ofclaim 16 wherein the multifunctional comonomer is a multifunctionaldiallylamine.
 20. The method of claim 19 wherein the multifunctionaldiallylamine is a bis(diallylamino)alkane or abis(diallylalkylammonio)alkane.
 21. The method of claim 20 wherein themultifunctional diallylamine is 1,10-bis(diallylmethylammonio)decanedibromide.
 22. The method of claim 15 wherein the polymer is crosslinkedby a bridging unit selected from the group consisting of straight chainor branched, substituted or unsubstituted alkylene groups,diacylalkylene groups, diacylarene groups and alkylene bis(carbamoyl)groups.
 23. The method of claim 22 wherein the bridging units areselected from the group consisting of —(CH₂)_(n)—, wherein n is aninteger from about 2 to about 20; —CH₂—CH(OH)—CH₂—; —C(O)CH₂CH₂C(O)—;—CH₂—CH(OH)—O—(CH₂)_(m) —O—CH(OH)—CH₂—, wherein m is 2 to about 4; —C(O)—(C₆H₂(COOH)₂)—C(O)—; and —C(O)NH(CH₂)_(p)NHC(O)—, wherein p is aninteger from about 2 to about
 20. 24. A method for removing bile acidsfrom a patient comprising the step of administering to the patient atherapeutically effective amount of a polymer characterized by adiallylamine monomer wherein the amino nitrogen atom is substituted withan ammonioalkyl group.
 25. The method of claim 24 wherein the polymercomprises a repeat unit of the general formula

wherein R¹ is hydrogen, a substituted or unsubstituted C₁-C₂₄-alkylgroup, a substituted or unsubstituted arylalkyl group or a substitutedor unsubstituted aryl group; R² is an ammonioalkyl group; and X⁻ is apharmaceutically acceptable anion.
 26. The method of claim 24 whereinthe polymer is characterized by a repeat unit of the general formula

wherein R is an ammonioalkyl group.
 27. The method of claim 24 whereinthe ammonioalkyl group is of the general formula

wherein n is an integer from 2 to about 20, X— is an anion, and R⁴, R⁵and R⁶ are each, independently, hydrogen or a C₁-C₂₄-alkyl group. 28.The method of claim 27 wherein at least one of R⁴, R⁵ and R⁶ is aC₆-C₂₂-alkyl group.
 29. The method of claim 25 wherein the polymercomprises from about 1 mole percent to 100 mole percent of thediallylamine repeat unit having an ammonioalkyl-substituted aminonitrogen atom.
 30. The method of claim 24 wherein the polymer iscrosslinked.
 31. The method of claim 30 wherein the polymer comprises amultifunctional comonomer.
 32. The method of claim 31 wherein themultifunctional monomer is selected from the group consisting ofdiacrylates, dimethacrylates, diacrylamides, dimethacrylamides andpolyvinylarenes.
 33. The method of claim 32 wherein the multifunctionalcomonomer is selected from the group consisting of ethylene glycoldiacrylate, propylene glycol diacrylate, butylene glycol diacrylate,ethylene glycol dimethacrylate, butylene glycol dimethacrylate,methylene bis(methacrylamide), ethylene bis(acrylamide), ethylenebis(methacrylamide), ethylidene bis(acrylamide), ethylidenebis(methacrylamide), bisphenol A dimethacrylate, bisphenol A diacrylate,diallylacrylamide and divinylbenzene.
 34. The method of claim 30 whereinthe multifunctional comonomer is a multifunctional diallylamine.
 35. Themethod of claim 34 wherein the multifunctional diallylamine is abis(diallylamino)alkane or a bis(diallylalkylammonio)alkane.
 36. Themethod of claim 35 wherein the multifunctional diallylamine is1,10-bis(diallylmethylammonio)decane dibromide.
 37. The method of claim30 wherein the polymer is crosslinked by bridging units selected fromthe group consisting of straight chain or branched, substituted orunsubstituted alkylene groups, diacylalkylene groups, diacylarene groupsand alkylene bis(carbamoyl) groups.
 38. The method of claim 37 whereinthe bridging units are selected from the group consisting of—(CH₂)_(n)—, wherein n is an integer from about 2 to about 20;—CH₂—CH(OH)—CH₂—; —C(O)CH₂CH₂C(O)—;—CH₂—CH(OH)—O—(CH₂)_(n)—O—CH(OH)—CH₂—, wherein n is 2 to about 4;—C(O)—(C₆H₂(COOH)₂)—C(O)—; and —C(O)NH(CH₂)_(p)NHC(O)—, wherein p is aninteger from about 2 to about
 20. 39. A polymer characterized by adiallylamine monomer wherein the amino nitrogen atom is substituted byan ammonioalkyl substituent.
 40. The polymer of claim 39, said polymercomprising a repeat unit of the general formula

wherein R¹ is hydrogen, a substituted or unsubstituted C₁-C₂₄-alkylgroup, a substituted or unsubstituted arylalkyl group or a substitutedor unsubstituted aryl group; R² is an ammonioalkyl group; and X⁻ is apharmaceutically acceptable anion.
 41. The polymer of claim 39, saidpolymer being characterized by a repeat unit of the general formula

wherein R is an ammonioalkyl group.
 42. The polymer of claim 39 whereinthe ammonioalkyl group is of the general formula

wherein n is an integer from 2 to about 20, X— is an anion, and R⁴, R⁵and R⁶ are each, independently, hydrogen or a C₁-C₂₄-alkyl group. 43.The polymer of claim 42 wherein at least one of R⁴, R⁵ and R⁶ is aC₆-C₂₂-alkyl group.
 44. The polymer of claim 40, said polymer comprisingfrom about 1 mole percent to 100 mole percent of the diallylamine repeatunit having an ammonioalkyl-substituted amino nitrogen atom.
 45. Thepolymer of claim 40, said polymer being crosslinked.
 46. The polymer ofclaim 45, said polymer comprising a multifunctional comonomer.
 47. Thepolymer of claim 46 wherein the multifunctional monomer is selected fromthe group consisting of diacrylates, dimethacrylates, diacrylamides,dimethacrylamides and polyvinylarenes.
 48. The polymer of claim 47wherein the multifunctional comonomer is selected from the groupconsisting of ethylene glycol diacrylate, propylene glycol diacrylate,butylene glycol diacrylate, ethylene glycol dimethacrylate, butyleneglycol dimethacrylate, methylene bis(methacrylamide), ethylenebis(acrylamide), ethylene bis(methacrylamide), ethylidenebis(acrylamide), ethylidene bis(methacrylamide), bisphenol Adimethacrylate, bisphenol A diacrylate, diallylacrylamide anddivinylbenzene.
 49. The polymer of claim 45 wherein the multifunctionalcomonomer is a multifunctional diallylamine.
 50. The polymer of claim 49wherein the multifunctional diallylamine is a bis(diallylamino)alkane ora bis(diallylalkylammonio)alkane.
 51. The polymer of claim 50 whereinthe multifunctional diallylamine is 1,10-bis(diallylmethylammonio)decanedibromide.
 52. The polymer of claim 45 wherein the polymer iscrosslinked by bridging units selected from the group consisting ofstraight chain or branched, substituted or unsubstituted alkylenegroups, diacylalkylene groups, diacylarene groups and alkylenebis(carbamoyl) groups.
 53. The polymer of claim 52 wherein the bridgingunits are selected from the group consisting of —(CH₂)_(n)—, wherein nis an integer from about 2 to about 20; —CH₂—CH(OH)—CH₂—;—C(O)CH₂CH₂C(O)—; —CH₂—CH(OH)—O—(CH₂)_(n)—O—CH(OH)—CH₂—, wherein n is 2to about 4; —C(O)—(C₆H₂(COOH)₂)—C(O)— and and —C(O)NH(CH₂)_(p)NHC(O)—,wherein p is an integer from about 2 to about
 20. 54. A method forremoving bile acids from a patient comprising the step of administeringto the patient a therapeutically effective amount of a crosslinkedpoly(diallylamine) polymer wherein more than 10% of the amino nitrogenatoms bear a C₃-C₂₄-alkyl group.
 55. The method of claim 54 wherein morethan 20% of the amino nitrogen atoms bear a C₃-C₂₄-alkyl group.